Novel hydroxy substituted prostanoic acids, esters, congeners, intermediates and process

ABSTRACT

This disclosure describes certain 11-hydroxy and 11-deoxy-9-keto(or hydroxy)-prostanoic acid derivatives useful as bronchodilators, anti-ulcer agents, or as intermediates.

CROSS REFERENCE TO RELATED APPLICATIONS

This is a division of application Ser. No. 922,285 filed July 6, 1978,which is in turn a division of application Ser. No. 806,871, filed May30, 1978 which is, in turn a CIP of Ser. No. 540,052 filed Jan. 10,1975, which is in turn a division of Ser. No. 355,349 filed Apr. 7, 1973now U.S. Pat. No. 3,873,607, which is in turn a division of Ser. No.274,768 filed July 24, 1972.

BRIEF SUMMARY OF THE INVENTION

This invention relates to novel hydroxy substituted prostanoic acids andderivatives as well as to intermediates and methods for theirpreparation. These methods embrace novel and useful procedures for thepreparation of prostaglandin E₁, 11-deoxyprostaglandin E₁,13-dihydroprostaglandin E₁, and other known biologically importantprostaglandin congeners. The novel compounds of this invention may berepresented by the following general formula: ##STR1## wherein n is aninteger having the value 1 or 2; R₁ is hydrogen, lower alkoxy,triphenylmethyl, or triphenylmethyl in which one or two of the phenylrings is substituted with an alkyl or an alkoxy group having up to 3carbon atoms; R₂ is a straight chain alkyl group having from 2 to 10carbon atoms, a straight chain alkyl group having from 2 to 10 carbonatoms and substituted with one or two alkyl groups each having from oneto three carbon atoms, a straight chain alkenyl group having from 3 to10 carbon atoms, a straight chain alkenyl group having from 3 to 10carbon atoms and substituted with one or two alkyl groups having betweenthem from 2 to 5 carbon atoms, or a straight chain alkynyl group havingfrom 3 to 10 carbon atoms; R₃ is hydroxy or an alkoxy group having from1 to 12 carbon atoms; Y is a divalent radical selected from the groupconsisting of those of the formulae: ##STR2## Z is a divalent radicalselected from the group consisting of those of the formulae: ##STR3##wherein m is an integer from 3 to 8, inclusive, p is an integer from 2to 6 inclusive, R₄ is an alkyl group having up to 3 carbon atoms, and R₅is an alkyl group having up to 3 carbon atoms, a fluorine atom, or aphenyl group; R₆ is hydrogen or an alkyl group having up to three carbonatoms; R₇ is hydrogen or an alkyl group having up to 3 carbon atoms; andthe moiety --C₁₃ -C₁₄ -- is ethylene, trans-vinylene, or cis-vinylene;with the first proviso that when n is 1, R₁ is hydrogen, R₇ Z is--(CH₂)_(m) -- and --C₁₃ -C₁₄ -- is ethylene or trans-vinylene then R₂does not include a straight chain alkyl group having from 2 to 10 carbonatoms; and with the second proviso that when Z is ##STR4## R₁ ishydrogen, R₂ is a straight chain alkyl group having from 2 to 10 carbonatoms and R₇ is hydrogen then --C₁₃ -C₁₄ -- is ethylene or cis-vinylene;and with the third proviso that when R₆ is alkyl then R₁ is hydrogen;and with the fourth proviso that only one unsaturated bond can bedirectly adjacent to C₁₅ ; and with the fifth proviso that when R₇ is analkyl group then the groups attached to the C₈ position may have the8α-alkyl(8-iso-configuration of the formula: ##STR5##

Embraced within the scope of the present invention are all the possibleoptical isomers of the above general formula. Also embraced within thescope of the present invention are the non-toxic, pharmaceuticallyacceptable salts of the novel compounds of the present invention when R₃is hydroxy. The cations comprised in these salts include, for example,the non-toxic metal cations such as the sodium ion, potassium ion,calcium ion, and magnesium ion as well as the organic amine cations suchas the tri(lower alkyl)amine cations (.e.g, triethylamine,triethanolamine) procaine, and the like.

The novel compounds of the present invention are usually obtainable asoils having characteristic absorption spectra. They are relativelyinsoluble in water but are relatively soluble in common organic solventssuch as ethanol, ethyl acetate, dimethylformamide, and the like. Thecationic salts of the compounds when R₃ is hydroxy are, in general,white to yellow crystalline solids having characteristic melting pointsand absorption spectra. They are relatively soluble in water, methanol,and ethanol but are relatively insoluble in benzene, diethyl ether, andpetroleum ether.

DETAILED DESCRIPTION OF THE INVENTION

The prostaglandins are a family of closely related compounds which havebeen obtained from various animal tissues, and which stimulate smoothmuscle, lower arterial blood pressure, antagonize epinephrine-inducedmobilization of free fatty acids, and have other pharmacological andautopharmacological effects in mammals. See Bergstrom et al., J. Biol.Chem. 238, 3555 (1963) and Horton, Experientia 21, 113 (1965) andreferences cited therein. All of the so called natural prostaglandinsare derivatives of prostanoic acid: ##STR6## The hydrogen atoms attachedto C-8 and C-12 are in trans-configuration. When the two side-chains (orthe C-8 and C-12 hydrogens) are cis to each other, the compounds arereferred to as 8-iso prostaglandins. The natural prostaglandinsrepresent only one of the possible optical isomers. The compounds ofthis invention include all possible optical isomers.

The novel compounds of the present invention may be readily preparedfrom certain cycloalkenone intermediates which may be represented by thefollowing general formula: ##STR7## wherein R'₃ is an alkoxy grouphaving from 1 to 12 carbon atoms; and n and Z are as hereinabovedefined.

The cycloalkenone intermediates may be readily prepared from2-carbethoxycyclopentanone or 2-carbethoxycyclohexanone in accordancewith the reaction schemes set forth in Flowsheets A, B, C, I and J.##STR8## wherein m and n are as hereinabove defined and X is iodo orbromo. In accordance with this reaction scheme, the cycloalk-2-en-1-ones(VIII) are developed by first converting 2-carbethoxycyclopentanone or2-carbethoxycyclohexanone (I) to the sodium enolates thereof by means ofsodium hydride in dimethoxyethane and then treating the sodium enolatewith an ethyl ω-haloalkanoate (II). There is thus obtained thecorresponding 2-carbethoxy-2-(ω-carbethoxyalkyl)cycloalkanone (III)which is then hydrolyzed and decarboxylated to afford the2-(ω-carboxyalkyl)cycloalkanone (IV). This acid is then esterified withethanol whereby the 2-(ω-carbethoxyalkyl)cycloalkanone (V) is obtained.The reaction conditions for carrying out the above sequence of reactionsare well known in the art. The conversion of the cycloalkanone (V) tothe enol acetate (VI) is effected by heating with acetic anhydride inthe presence of p-toluenesulfonic acid. Preparation of the enol acetate(VI) usually requires heating for a period of from about eight tothirty-six hours. During this period, it is preferable to allowby-product acetic acid to distill out in order to force the reaction tocompletion. The bromination of the enol acetates (VI) to the2-bromocycloalkanones (VII) is preferably carried out in a two phasesystem as follows. A solution of bromine in chloroform is added to arapidly stirred mixture of a solution of the enol acetate (VI) inchloroform and an aqueous solution of an acid acceptor such as calciumcarbonate or soda ash. This addition is carried out at 0° -5° C. over aperiod of about half an hour, stirring is continued for an additionalperiod of about half an hour to a few hours, and the product (VII) isthen isolated by standard procedures. The dehydrobromination of the2-bromocycloalkanones (VII) is preferably carried out indimethylformamide with a mixture of lithium bromide and lithiumcarbonate at the reflux temperature for a period of about 30 minutes toan hour or so. The so formed cycloalk-2-en-1-ones (VIII) are alsoisolated by standard procedures well known in the art. Substitution ofX--(CH₂)_(m) --C(R₄)₂ --CH₂ --CO₂ C₂ H₅ for (II) in Flowsheet A andcarrying through the sequence of transformations illustrated therein isproductive of the following cycloalk-2-en-1-one (VIIIa): ##STR9##wherein X, n, m and R₄ are as hereinabove defined.

The required cycloalk-2-en-1-one intermediates of general structure(XVI), wherein the side-chain has a lower alkyl group, fluorine atom orphenyl group alpha to the carbethoxy function, may be prepared inaccordance with the following reaction scheme: ##STR10## wherein n, mand R₅ are as hereinabove defined and G is a lower alkyl or aryl group.In accordance with this reaction scheme, the2-(ω-carbethoxyalkyl)cycloalk-2-en-1-ones (IX) are converted to thecorresponding 1-methoximino-2-(ω-carbethoxyalkyl)-2-cycloalkenes (X) bytreatment with methoxyamine. With the ring carbonyl function thusblocked it is possible to effect a preferential reduction of the estergroup by treatment with diisobutylaluminum hydride. The resultingalcohol (XI) is converted to a tosylate derivative (XII), whichundergoes displacement on treatment with the sodium salt of a diethyl R₅-substituted malonate (XIII) to provide the disubstituted malonatederivatives (XIV). Hydrolysis and decarboxylation as well asconcomittant cleavage of the methoximino blocking group provides thedesired 2-(ω-carboxy-ω-R₅ -substituted-alkyl)cycloalk-2-en-1-ones (XV),which are readily converted to the corresponding ester (XVI) by theusual procedure via the acid chloride and subsequent treatment with theappropriate alcohol in the presence of a tertiary amine.

The requisite 2-(ω-carbethoxy-ω-1-oxa-alkyl)cycloalk-2-en-1-ones (XXII)and 2-(ω-carbethoxy-ω-1-thia-alkyl)cycloalk-2-en-1-ones (XXVI) may beprepared in accordance with the reaction schemes of Flowsheet C, whereinn and m are as hereinbefore defined. ##STR11##

In accordance with the reaction scheme shown in Flowsheet C, for thepreparation of the oxa derivative (XXII), an appropriate2-(ω-carbethoxyalkyl)cycloalk-2-en-1-one (XVII) is converted to thecorresponding methoxime (XVIII), the ester function of which is thenpreferentially reduced with diisobutylaluminum hydride to afford themethoxime alcohol (XIX). The alcohol (XIX) is converted on treatmentwith n-butyl lithium to the lithio alcoholate, which then is O-alkylatedby reaction with ethyl bromoacetate to provide (XX). Hydrolysis withacetone-aqueous hydrochloric acid furnishes the deblocked keto-acid(XXI), which is then re-esterified with ethanol in the presence ofp-toluenesulfonic acid to give the required2-(ω-carbethoxy-ω-1-oxa-alkyl)cycloalk-2-en-1-one (XXII). O-Alkylationcan also be accomplished by treatment of the lithio alcoholate of (XIX)with sodium or other metal salt of bromoacetic acid, in which case thefree carboxylic acid corresponding to ester (XX) is obtained. Hydrolysisas for (XX) provides the keto acid (XXI).

The preparation of the thia derivative (XXVI), proceeds from theintermediate alcohol (XIX), which after conversion to the tosylateintermediate (XXIII) and reaction with the sodium salt of ethylmercaptoacetate furnishes intermediate (XXIV). Deblocking of XXIV withacetone-aqueous hydrochloric acid provides the keto-acid (XXV), which onre-esterification with ethanol gives the required2-(ωcarbethoxy-ω-1-thia-alkyl)cycloalk-2-en-1-ones (XXVI).

Certain of the 11-deoxy-9-keto(or hydroxy)-prostanoic acid derivativesof this invention, as defined in the general formula on page 1 above,may be prepared from cycloalkenone (XXXI) and the triphenylmethoxysubstituted 1-alkyne (XXVII) as depicted in Flowsheet D. In Flowsheet D,n, R₃, R'₃ and Z are as hereinabove defined; R'₂ is a straight chainalkyl group having from 2 to 10 carbon atoms, a straight chain alkylgroup having from 2 to 10 carbon atoms and substituted with one or twoalkyl groups each having from one to three carbon atoms, a straightchain alkenyl methyl group having from two to nine carbon atoms, or astraight chain alkenyl methyl group having from two to nine carbon atomsand substituted with one or two alkyl groups having between them 2 to 5carbon atoms; and R is a lower alkyl group. ##STR12##

In accordance with the reaction scheme of Flowsheet D, thetriphenylmethoxy substituted 1-alkyne (XXVII) is treated withdiisobutylaluminum hydride (XXVIII). This reaction of the 1-alkyne(XXVII) with diisobutylaluminum hydride (XXVIII) provides the alane(XXIX) containing the trans-double bond and is carried out in an inertsolvent such as benzene, toluene, and the like at temperatures in therange of 40°-60° C. for several hours. It can also be carried out in asolvent such as tetrahydrofuran, usually in an approximate 2:1 mixturewith benzene or hexane; in which case the reaction requires somewhatmore vigorous conditions, usually treating at about 70°-75° C. for abouteighteen hours. The subsequent reaction with methyl or n-butyl lithium(R-Li) is preferably carried out in a mixture of the above solvents withan ether-type solvent such as diethyl ether, dibutyl ether,tetrahydrofuran and the like. This reaction is rapid and is preferablycarried at 0°-10° C. with cooling. The conjugate 1,4-addition of theresulting alanate salt (XXX) to the cycloalk-2-en-1-one (XXXI) ispreferably carried out at ambient temperatures for a period of 12 to 24hours. This reaction is also best carried out in an ether-type solventsuch as diethyl ether, dibutyl ether, tetrahydrofuran, and the like. Theintermediate alanate-enolate adduct is then carefully hydrolyzed in situwith dilute hydrochloric acid with cooling, and the products (XXXII) areisolated in the usual manner well known in the art. Removal of thetriphenylmethyl blocking group can then be accomplished by treating withweak acid. A preferred procedure involves heating at 45° C. for 3.5hours in a solvent system consisting of aceticacid:tetrahydrofuran:water in the proportion of 4:2:1. Saponification inthe usual manner of the resulting alkyl ester (XXXIII, R₃ =alkoxy)provides the corresponding carboxylic acid (XXXIII, R₃ =OH).

All available evidence leads us to the conclusion that in the product(XXXIII) the two side-chains attached to C₈ and C₁₂ are trans to eachother. However, we are not certain of the configurational relationshipin product (XXXII) as it is obtained directly from the alanate process.These products may have the side-chains in a trans or cis relationshipor they may be a mixture containing both the trans- and cis-isomers.This is indicated in the nomenclature of the compounds involved by thedesignation of 8ξ. In order to ensure a trans-relationship in both(XXXII) and (XXXIII) these products can be submitted to conditions knownin the literature to equilibrate the cis-8-iso-PGE₁ to a mixturecontaining about 90% of the trans product. These conditions involvetreatment with potassium acetate in aqueous methanol for 96 hours atroom temperature.

The triphenylmethyl blocking group for the hydroxy function in (XXVII)etc. is an important feature of this process and other oxygen blockinggroups, e.g., tetrahydropyranyl and alkyl, are not compatible with aclean cis-addition of diisobutyl aluminum hydride (XXVIII) to the alkyne(XXVII) to provide the desired trans-vinyl function. Alternativeprocedures for the preparation of novel lithio alanate reagents usefulfor the introduction of the Δ¹³ -trans 15-oxy β-chain by conjugate1,4-addition are illustrated in Flowsheet K further below.

The intermediates for the introduction of the Δ¹³ -15-hydroxy side-chainare an integral part of this invention and they may be represented bythe following general formulae (A), (B), (C), (D) and (E) wherein R'₂ isas hereinabove defined, R is a lower alkyl group, not necessarily thesame for each use, and R' is an alkyl group having from one to tencarbon atoms not necessarily the same for each use, W₁ is lower alkoxy,triphenylmethyl, or a triphenylmethyl group in which one or two of thephenyl rings is substituted with a lower alkoxy group; W₂ is loweralkoxy, triphenylmethyl, a triphenylmethyl group in which one or two ofthe phenyl rings is substituted with a lower alkoxy group,tetrahydropyranyl, α-(lower alkoxy) substituted lower alkyl, t-butyl, ora tri(lower alkyl)silyl group; X₁ is iodo or bromo; s is an integerhaving the value of one to three inclusive, and t is an integer havingthe value of one to three inclusive, with the proviso that the sum of sand t must be equal to four. ##STR13##

The alanate conjugate addition procedure is also useful for thesynthesis of prostaglandin E₁ (XL) as illustrated in Flowsheet E. Thisreaction sequence is carried out in the same manner as described for thesequence in Flowsheet D. It is to be noted that the introduction of theΔ¹³ -15-oxy chain proceeds trans to the 11-oxy function. For thissynthesis, it is best to use the tetrahydropyranyl or trialkylsilylesters, since these esters can be hydrolyzed under conditions compatiblewith the stability of the β-ketol feature of prostaglandin E₁. Alkylesters would be hydrolyzed by fermentation with Baker's Yeast. Thetetrahydropyranyl or trialkylsilyl, and triphenylmethoxy blocking groupsare removed by mild acid treatment, for example with aceticacid:tetrahydrofuran:water (4:2:1) as described hereinabove. Applicationof the lithio alanate conjugate addition process to the synthesis ofprostaglandins E₂ and E₃ is described below in connection with FlowsheetN. ##STR14##

The 13-dihydro derivatives (C₁₃ -C₁₄ is ethylene) of this invention canbe prepared by reduction of the Δ¹³ function in the corresponding13-prostenoic acids or esters. This reduction can be accomplished byhydrogenation. However this procedure is not cleanly applicable in thepresence of other double bonds in the molecule. In the latter instancethe 13-dihydro derivatives are preparable via conjugate addition of aGrignard derivative (XLII) to cycloalkenone (XLI) in the presence of acatalyst such as the tributylphosphine-cuprous iodide complex as setforth in Flowsheet F, wherein n, Z, R₂ and R'₃ are as hereinabovedefined; Q is a blocking group; and X is chlorine, bromine or iodine,preferably bromine or iodine. The blocking group (Q) for the hydroxylfunction in (XLII) can be any group stable to the Grignard reagent andwhich can later be removed by chemical treatment (e.g., mild hydrolysisor catalytic hydrogenolysis in the absence of carbon to carbon doublebonds elsewhere in the molecule) to which the remainder of the moleculeis stable. Suitable blocking groups, therefore, may be, for example,benzyl, diphenylmethyl, triphenylmethyl, tetrahydropyranyl, or a moietyof the formula: ##STR15## wherein R₁₁ is hydrogen, methyl or ethyl.Among the above-described blocking groups, we have found tert-butyl tobe particularly convenient and useful. ##STR16##

In accordance with the above reaction scheme, the conjugate 1,4-additionof a 3-(substituted hydroxy)alkyl or alkenyl magnesium halide (XLII) toa cycloalk-2-en-1-one (XLI) is carried out in the presence of acatalyst. In general, Grignard reactions with conjugated ketones provide1,2-addition products; conjugate 1,4-addition is usually accomplishedwhen the reaction is carried out in the presence of a cuprous chlorideor cuprous acetate catalyst. It is therefore most unexpected that thereaction of the cycloalkenone (XLI) with a Grignard reagent (XLII) inthe presence of either of the aforementioned catalysts does not giveappreciable amounts of the desired 1,4-conjugate addition products. Thenovel feature of our process is provided by the use, as a catalyst, of acuprous halide complex with a trisubstituted phosphine, a trialkylphosphonate, a tertiary amine or a heterocycle containing a basicnitrogen (e.g., pyridine). We have found it preferable to usetributylphosphine-cuprous iodide complex; (C₄ H₉)₃ P.CuI. The reactionis best carried out in the usual way in an ether-type solvent such asdiethyl ether, dibutyl ether, tetrahydrofuran, and the like, at roomtemperature for a period of time of from two to eighteen hours. Theintermediate magnesium halide-enolate adduct is then hydrolyzed in situ,preferably with ammonium chloride, at room temperature and the product(XLIII) is isolated in the usual manner well known in the art.

When the blocking group is a tertiary alkyl moiety such as tert-butyl,deblocking of (XLIII) to afford (XLIV) is conveniently effected bytreatment with glacial trifluoroacetic acid at from -5° C. to 10° C. fora period of one to three hours. Since this procedure may lead to partialtrifluoroacetylation of the free hydroxy function, it is preferablyfollowed by treatment with aqueous ammonia (about 1.0 N concentration)for about 15 minutes at ambient temperatures. When the blocking group istetrahydropyranyl, its removal is readily effected with dilute acid.When the blocking group is a moiety such as benzyl, diphenylmethyl ortriphenylmethyl, deblocking of (XLIII) is conveniently effected bycatalytic hydrogenolysis, procedures for which are well known in theart. In the instance of triphenylmethyl, deblocking is preferablyeffected by treating with acetic acid:tetrahydrofuran:water (4:2:1) atabout 45° C. for about 3.5 hours.

Mild acid treatment results in hydrolysis of the tetrahydropyranylesters; alkyl esters can be hydrolyzed by the usual saponificationtechniques.

When the cycloalkanone esters (XLIII) are formed by quenching of thereaction mixture with aqueous ammonium chloride solution, the relativestereochemical relationship of the two side-chains is not known withcertainty. Therefore, the bond linking the Grignard-derived side-chainto the cycloalkyl ring is indicated by a ˜ bond in (XLIII). However, inany case, the subsequent deblocking and ester hydrolysis proceduresensure the development, at least in predominant proportion, of thethermodynamically favored trans-relationship between the twoside-chains, as is depicted in structure (XLIV) of the reaction scheme.

An alternative method for the introduction of the Δ¹³ -15-hydroxyside-chain involves 1,4-conjugate addition to cycloalkenone (LV) of avinyl Grignard reagent [(LIII)+(LIV)] in the presence of a catalyst suchas the tributylphosphine cuprous iodide complex followed by deblocking.From this process, in addition to the product (LVIII) containing the C₁₃-C₁₄ moiety as a trans-vinylene function there also is obtained thecorresponding product (LIX) in which the C₁₃ -C₁₄ moiety is acis-vinylene function. These novel cis-Δ¹³ derivatives are also embracedwithin the scope of this invention. The reaction sequence for the"vinyl" Grignard process is illustrated in flowsheet G, which follows,and in which W₂, n, Z, R₃ and R'₃ are as hereinabove defined, and R"₃ isa straight chain alkyl group having from 2 to 10 carbon atoms, or astraight chain alkyl group having from 2 to 10 carbon atoms andsubstituted with one or two alkyl groups having from one to three carbonatoms. ##STR17##

In accord with the reaction sequence of Flowsheet G the vinyl Grignardreagent (LIII+LIV), is prepared under an inert atmosphere in arelatively limited amount of anhydrous tetrahydrofuran. More vigorousconditions (e.g., heating in an oil bath at 70°-80° C., one hour), forthe formation of the Grignard reagent (LIII+LIV) favors the proportionof Δ¹³ -cis isomer (LIX) in the product of conjugate addition. Milderconditions (for example 35°-47° C., one hour) favors the proportion ofΔ¹³ -trans isomer (LVIII) in the final product.

Conjugate addition of the vinyl Grignard reagent mixture [(LIII)+(LIV)]to cycloalkenone (LV) is then preferably carried out by addition of theGrignard to the cycloalkenone dissolved in an ether type solvent, e.g.,diethylether, containing a catalyst such as thetributylphosphine-cuprous iodide complex at a temperature of about 0° C.After a period of about thirty minutes to three hours the reactionmixture is poured onto aqueous concentrated ammonium chloride solutionto give (LVI)+(LVII). As explained hereinabove, at this stage therelationship of the two side-chains to each other is not determined. Inany event, deblocking the 15-hydroxy function with weak acid (whichprocedure also hydrolyzes trialkylsilyl or tetrahydropyranyl esters)provides the product (LVIII) and (LIX) in which the chains are trans toeach other. In the instance of alkyl esters, saponification provides thecorresponding carboxylic acids. The Δ¹³ -cis and Δ¹³ -trans-isomers canbe separated from each other by the usual techniques of chromatography;particularly useful is liquid-liquid partition chromatography.

The precursor 3-hydroxy-1-trans-alkenyl bromides (LI) can be prepared,as illustrated in Flowsheet G, by condensation of acetylene (XLV) withan acid chloride (XLVI) in the presence of aluminum trichloride. Theresulting 3-oxo-1-chloro-trans-1-alkylene (XLVII) is then converted tothe corresponding 1-bromo derivative (XLVIII), by reaction with excesslithium bromide. This reaction is preferably carried out in ketonesolvents, such as 2-pentanone or acetone. Reduction of the 3-ketofunction in (XLVIII), with for example, sodium borohydride provides thealcohol (LI). The alcohol function is then blocked to give (LII).Alternatively, the 3-oxo vinyl bromide (XLVIII) can be prepared directlyfrom the acyl bromide (L) and acetylene (XLIX) in the presence ofaluminum tribromide, preferably in ethylene dibromide.

The "vinyl Grignard" procedure outlined in Flowsheet G represents anovel, useful and convenient procedure for the synthesis of13-prostenoic acids and the novel Grignard reagents represented byformulae (LIII) and (LIV) are to be considered as embraced within thescope of this invention.

The "vinyl Grignard" technique can also be applied to a useful synthesisof prostaglandin E₁ and the novel Δ¹³ -cis-prostaglandin-E₁ asillustrated in Flowsheet H, below. Thus, treatment of cyclopentenone(LX) with Grignard [(LXI+(LXII)] in accordance with the considerationsdiscussed hereinabove, provides the conjugate addition products (LXIII)plus (LXIV), mild acid hydrolysis of which furnishes prostaglandin E₁(LXV) and Δ¹³ -cis prostaglandin E₁ (LXVI), separable by chromatography.##STR18##

The preparation of the cycloalkenone intermediates (LXXVI, LXXVII)bearing a cis double bond in the carboxylic acid side chain can beaccomplished by the sequence illustrated in Flowsheet I, which followsand in which n and p are as hereinabove defined. ##STR19##

In the above flowsheet I, the sequence wherein a2-carbalkoxycycloalkanone (LXVII) is transformed to a2-(β-hydroxyethyl)cycloalk-2-en-1-one (LXXIII) is carried out in themanner described in Flowsheet A. Methyl ether cleavage of thecorresponding 2-(β-methoxymethyl)cycloalkenone is achieved by treatingwith boron tribromide. Oxidation of the alcohol (LXXIII) with Collinsreagent [chromium trioxide-pyridine complex in methylene chloride underanhydrous conditions; J. C. Collins, W. W. Hess, and F. J. Frank,Tetrahedron Letters, 3363 (1968)] provides the aldehyde (LXXIV), whichis then treated in anhydrous dimethylsulfoxide with the ylid (LXXV)prepared from an (ω-carboxyalkyl)triphenyl phosphonium bromide andsodium hydride. The use of dimethylsulfoxide as a solvent for thisreaction leads to the predominant formation of the desired cis doublebond derivative (LXXVI). The acid function is (LXXVI) can be esterifiedin the usual fashion; with diazomethane, the methyl ester (LXXVII) isobtained.

Cyclopentenones such as (LXXVI wherein n=1) may also be prepared by thesequence illustrated in Flowsheet J, which follows and in which p is ashereinabove defined. ##STR20##

In Flowsheet J above the bicyclic hemiacetal (LXXVIII) [P. A. Grieco,Journ. Org. Chem., 37, 2363 (1972)] is treated with ylid (LXXIX) to givethe 1-hydroxy-3-cyclopentene (LXXX). Oxidation with Jones reagent givesthe corresponding ketone (LXXXI), which on base treatment furnishes therequired cyclopentenone (LXXXII), which can then be esterified in theusual manner.

Certain of the intermediates illustrated in Flowsheets I and J, inparticular the compounds of formulae (LXXI), (LXXII), (LXXIII), (LXXIV),(LXXVI) (LXXVII) (and related esters), (LXXX) and (LXXXI) are novel anduseful compounds and are embraced within the scope of this invention.

Alternative procedures for the preparation of the alanate intermediatesto that discussed in connection with Flowsheet D above are illustratedbelow in Flowsheet K, wherein R', R'₂, R"₂ and W₂ are as hereinabovedefined. ##STR21##

In accordance with the sequence of Flowsheet K above the1-iodo-trans-1-alkenyl-3-oxo derivative (LXXXIV) is prepared by iodideinterchange, preferably in acetone or similar ketone, from thecorresponding chloride (LXXXIII), the preparation of which is describedin connection with Flowsheet G above. Reduction of (LXXXIV) to thealcohol (LXXXVI) can be accomplished in the usual manner with sodiumborohydride. The hydroxy function is then blocked to give (LXXXV,R'_(2-R") ₂). Treatment of the acetylene, ##STR22## with one equivalentof disiamylborane (prepared in situ from diborane and 2-methyl-2-butene)and then with excess anhydrous trimethylamine oxide followed bytreatment with an aqueous solution of excess sodium hydroxide and atetrahydrofuran solution of excess iodine is also productive of (LXXXV).Treatment of the trans-1-alkenyl iodide (LXXXV) at low temperatures,preferably at about -30° C. to -78° C., in an inert solvent, e.g.,hexane or toluene, with an alkyl lithium, e.g., butyl lithium, providesthe trans-1-alkenyl lithium reagent (LXXXVII). Treatment of this lithioderivative with a tri-alkyl aluminum furnishes the trans-1-alkenyltrialkyl alanate (LXXXVIII). Treatment of a dialkyl aluminum chloridewith two molar equivalents of lithio reagent (LXXXVII) gives thebis(trans-1-alkenyl)dialkyl alanate (LXXXIX) and treatment of analkylaluminum dichloride with three molar equivalents of lithio reagent(LXXXVII) affords the tris(trans-1-alkenyl)alkyl alanate (XC).

Each of the three types of alanates, (LXXXVIII), (LXXXIX) and (XC), canbe utilized for 1,4-conjugate addition reactions as describedhereinabove in connection with Flowsheets D and E above. Thus,substitution of (LXXXVIII), (LXXXIX) or (XC) for alanate (XXX) inFlowsheet D will provide the indicated products of the Flowsheet.Similarly, substitution of (LXXXVIII), (LXXXIX) or (XC) in which R₂ ' isn-pentyl for alanate (XXXVII) in Flowsheet E provides prostaglandins E₁.In general the mono alkenyl alanate (LXXXVIII) is preferred because itis more economical in the use of vinyl halide.

With regard to the cycloalkenones of Flowsheets D, E, F, G and H itshould be noted that the blocking groups for the 4-hydroxy function aswell as for the carboxylic acid may also be a tri-alkylsilyl group,e.g., trimethylsilyl, dimethyl-t-butylsilyl or dimethylisopropylsilyl.Cyclopentenones blocked in this manner are illustrated below in formula(XCI) and (XCII) wherein m, n, Z and R' (not necessarily the same foreach use) are as hereinabove defined. ##STR23##

All the novel products of this invention exclusive of certainintermediates bear a hydroxy or oxy function substituted at or at whatultimately becomes the C₁₅ atom of the product prostanoic acids andesters. Thus in at least most instances a 15-"normal" and a 15-"epi"racemate is obtained in at least near equal proportions. Each of theracemates contains equal amounts of the enantiomer wherein C₁₅ is in theS configuration and the enantiomer wherein it is in the R configuration.The racemates are separable from each other by the usual techniques ofchromatography. Also, resolution in the usual way of the β-chainprecursor for example, the resolution of 3-hydroxy-1-octyne is describedin the literature [see, R. Pappo, P. Collins and C. Jung. Ann. N.Y.Acad. of Science, 180 (Prostaglandins), 64(1971); J. Fried et al., ibid,p. 381]. Resolution prior to the conjugate addition operation willprovide the diastereomers wherein the C₁₅ atom is either in the 15(S) or15(R) configuration, as desired. Separation of the diastereomers soobtained, for example, by chromatography, will give the fully resolved(d and l) products provided there are no asymmetric carbon atoms otherthan at C₈ and C₁₂. The presence of other asymmetric sites requiresadditional resolution steps in order to obtain a single atipode. Thecompounds of this invention embrace all possible optical isomers.

The 11-deoxy-9-keto derivatives (XCIV) of this invention can beconverted to the corresponding 9-hydroxy derivatives. If this conversionis effected with sodium borohydride, the product is a mixture of 9α- and9β-hydroxy derivatives (XCIII) and (XCV) as set forth in the followingreaction scheme: ##STR24## wherein R₂, R₃, R₆, R₇, Z, n and --C₁₃ -C₁₄-- are as hereinabove defined. In general, when the reaction is carriedout with lithium perhydro-9b-boraphenalyl hydride [H. C. Brown and W. C.Dickson, Journ. Amer. Chem. Soc., 92, 709 (1970)] the product is atleast predominantly the 9α-hydroxy derivative (XCIII), wherein the9-hydroxy group is cis to the side-chain attached to C₈.

In accordance with accepted convention, an α-substituent at the 8-, 9-,or 12-positions is behind the plane of the paper whereas a β-substituentat these positions is in front of the plane of the paper. This isusually represented by a --bond for an α-substitutent, a --bond for aβ-substituent, and a bond where both are indicated. Thus, the 9-hydroxyderivatives may be variously represented as follows: ##STR25##

A useful procedure for the introduction of the 15-lower alkyl group (R₆)is illustrated by the sequences of Flowsheet M, which follows. ##STR26##

In Flowsheet M above n, Z, R₂, R₇ and R₆ are as hereinabove defined. Inthe sequence depicted in Flowsheet M the 9,15-diol (XCVI) is treatedwith 2,3-dichloro-5,6-dicyanobenzoquinone (DDQ) (XCVII), whichpreferentially oxidizes the allylic alcohol function at C₁₅ to give the15-ketone (XCVIII). Blocking of the remaining hydroxy function as atrimethylsilyl ether gives (IC) which is reacted with the alkylGrignard, R₆ MgI, to give the 15-alkyl-15-hydroxy derivative (CI).Hydrolysis of the silyl ether blocking group then gives the diol ester(C), saponification of which gives (CII). Oxidation of the secondary9-hydroxy function in (C) provides the 15-alkyl-9-oxo ester (CIII),saponification of which furnishes (CIV). (A similar sequence can beeffected with the Δ¹³ -cis-series.)

The processes of this invention are also useful for the preparation ofprostaglandin E₂ and prostaglandin E₃ and thus also PGF₂α and PGF₃α byreduction, for example with lithium perhydro-9b-boraphenalyl hydride.The 4-hydroxycyclopentenone intermediate (CXI) required for thesesyntheses is prepared in accordance with the procedure illustrated inFlowsheet N which follows and in which is also shown the transformationof this compound to prostaglandins E₂ and E₃. In Flowsheet N, J is anappropriate blocking group for the hydroxy and ester function in (CXI)which is compatible with the conjugate addition reaction and also isultimately removable by acid-catalyzed hydrolysis or other techniqueswhich will not disrupt the sensitive 11-oxy-9-keto system in theproducts (CXIII), (CXV), (CXVIII) and (CXVII). Particularly useful forthis purpose are the tetrahydropyranyl group and various trialkylsilylgroups (e.g., dimethylisopropylsilyl, trimethylsilyl,dimethyl-t-butylsilyl and the like. ##STR27##

In accordance with the above reaction scheme the 3,4-epoxylactol (CV)[E. J. Corey and R. Noyori, Tetrahedron Letters, 311 (1970)] is treatedwith the ylide (CVI) to give the 3,4-epoxycyclopentanol (CVII) bearingthe α-chain of the prostaglandin 2 series. Oxidation (for example withH₂ CrO₄.H₂ SO₄ -ether or Jones reagent) of (CVII) provides the epoxyketone (CVIII), mold base treatment of which results in the initialformation of the 4-hydroxycyclopent-2-en-1-one (CXI) and the isomeric3-hydroxycyclopent-4-en-1-one (CX) as a mixture. Further treatment ofthis mixture with dilute base under mild conditions (preferably pH10.3-10.6 for 24 hours) results in the isomerization of the 3-hydroxyisomer (CX) to the desired (CXI). We believe that the transformation ofthe epoxy ketone (CVIII) to the hydroxycyclopentenones (CX) and (CXI)and the isomerization of (CX) to (CXI) may take place through theintermediacy of the 3,4-diol (CIX). It is also conceivable thatisomerization of (CX) to (CXI) procedes via the epoxy derivative (CVIII)or the corresponding α-epoxide (CXIb); it is further conceivable that(CVIII) procedes to (CX) and (CXI) directly without the intermediacy of(CIX). Another possible intermediate for the isomerization of (CX) to(CXI) is the corresponding diene (CXIa). The preparation of (CXI) isalso possible via the α-epoxide series from (CXIc) via the α-epoxidecorresponding to (CVII) and (CVIII) such as (CXIb) or via a mixture ofthe α and β epoxides. In practice, it is most convenient to utilize amixture of α- and β-epoxides (CXIc and CV). The hydroxy and acidfunction in the 4-hydroxycyclopentenones (CXI) are then appropriatelyblocked to give (CXII). Appropriate blocking groups aretetrahydropyranyl, trimethylsilyl, dimethyl-isopropylsilyl,dimethyl-t-butylsilyl and the like. Treatment of (CXII) with the lithioalanate (CXIV) or its equivalent (see the discussion hereinabove forFlowsheets K and E) gives the conjugate addition product (CXIII) inwhich the configuration at C₈ is undetermined. Mild acid treatment, forexample with acetic acid:tetrahydrofuran:water, (4:2:1), of (CXIII)results in the removal of blocking groups, and if necessaryequilibration to the all-trans configuration, to give prostaglandin E₂(CXV). Similarly treatment of (CXII) with the lithio alanate (CXVI)gives prostaglandin E₃ (CXVII).

Substitution in Flowsheet N, of ylide (CXIX), wherein p is ashereinabove defined, for the ylide (CVI) provides, by transformationsanalogous to those described in Flowsheet N [(CV) to (CXI) and (CXII)],the 4-hydroxycyclopent-2-en-1-ones (CXX) and their blocked ether-esters(CXXI). These novel and useful intermediates are a part of the presentinvention. ##STR28##

The 8β-lower alkyl group (R'₇) is introduced as illustrated in FlowsheetO below via the bromomagnesium enolate (CXXV). This novel and usefulintermediate is obtained by conjugate addition of the 1-alkenyl Grignardreagent [(CXXIII)+(CXXIV)], preferably prepared at about 35° C., to thecycloalkenone (CXXII) in the presence of a catalyst such as thetri-n-butylphosphine cuprous iodide complex as described hereinabove inconnection with Flowsheets G and H. It is also possible to utilize forthese purposes in an analogous manner the magnesio enolate (CXXVIII)obtained by conjugate addition of Grignard (XLII) to cycloalkenone (XLI)as described hereinabove in connection with Flowsheet F, in which casethe 13,14-dihydro derivative of this invention are obtained. InFlowsheet O below, n, Z, R₃, R'₃, R'₂, W₂, R₂, Q and X are ashereinabove defined and R'₇ is an alkyl group having up to 3 carbonatoms. When the magnesio enolate (CXXV) is treated with a lower alkylhalide, e.g., methyl iodide, it undergoes alkylation at the 8β -siteproviding, after deblocking of the 15-oxy group in intermediate (CXXVI),the 8β-alkyl derivative (CXXVII). In the instance of alkyl esters,saponification gives the corresponding carboxylic acids (CXXVII, R₃═OH). The compounds corresponding to (CXXVII) wherein C₁₃ -C₁₄ is acis-vinylene double bond are preferably prepared by utilizing the vinylGrignard reagent prepared at temperatures in the range of 70°-75° C., asdiscussed hereinabove (Flowsheets G and H).

Also obtained from the alkylation of (CXXV) is the 8α-alkyl-8-isoderivative corresponding to (CXXVI), which after deblocking provides the8α-alkyl-8-iso-products (CXXIX). Usually the 8α-product is formed to asignificantly lesser extent than the 8β-product (CXXVI). The 8α and 8βproducts are seperable from each other by the usual techniques ofchromatography. ##STR29##

Application of the S-alkylation process to the 11-oxy series providesthe novel compounds of formula (CXXX), wherein R₁, R₂, R₆, Y and C₁₃-C₁₄ are as hereinabove defined and wherein R'₇ is an alkyl group havingup to 3 carbon atoms, R₈ is selected from the group consisting ofhydrogen, lower alkanoyl, tetrahydropyranyl and tri-lower alkylsilylgroups, R₉ is selected from the group consisting of hydroxy, alkoxyhaving from 1 to 12 carbon atoms, tetrahydropyranyloxy and tri-loweralkyl silyloxy groups, Z₂ is a divalent radical selected from the groupconsisting of those of the formulae: ##STR30## wherein m, p, R₄ and R₅are as hereinabove defined; and the moiety ##STR31## when Y is ##STR32##can also be the divalent radical ##STR33## with the proviso that onlyone unsaturated bond can be directly adjacent to C₁₅ ; and with thesecond proviso that when R₆ is alkyl then R₁ is hydrogen; and with thethird proviso that the groups attached to C₈ may be in the 8β-alkyl(8-iso) configuration: ##STR34##

The novel compounds of formula (CXXX) are also embraced by thisinvention. The preparation of these compounds may be illustrated by thereaction of Flowsheet P below, wherein R₉, Z₂, W₂, R"₂, R'₇ and R₃ areas hereinabove defined and R'₈ has all the possibilities defined abovefor R₈ except that it is not hydrogen. ##STR35##

In accordance with the sequence of Flowsheet P above, treatment of theether-ester 4-oxycyclopentenone (CXXXI) with the 1-alkylene Grignardreagents [(CXXIII)+(CXXIV)] (see Flowsheet O) gives the bromomagnesioenolate (CXXXII). This operation also results in the introduction of thetrans C₁₃ -C₁₄ double bond (as shown in CXXXII), as well as thecorresponding compound with the cis-double bond. The trans bond isfavored when the Grignard is prepared at lower temperatures, about 35°C.; the cis-bond at higher temperatures, about 70°-75° C. This point ismore fully discussed above in connection with Flowsheets G and H. Themagnesio enolate (CXXXII) is a key intermediate and when it is treatedwith a lower alkyl halide, e.g. methyliodide, it undergoes alkylation togive the 8β-lower alkyl derivative (CXXXIII). Deblocking of the15-hydroxy blocking group (.e.g., triphenylmethyl), and of the11-hydroxy tetrahydropyranyl or trialkylsily ether blocking groups aswell as of the tetrahydropyranyl or trialkyl silyl esters isaccomplished under mild acid conditions, e.g. heating at 45° C. for 3.5hours in a solvent system consisting of aceticacid:tetrahydrofuran:water (4:2:1). This procedure provides (CXXXV). Thecompounds of structure (CXXXV) or (CXXXIII) can be converted to 8β-alkylprostaglandins of the A class (CXXXIV) by treatment with acid or base, apreferred procedure involves treatment in tetrahydrofuran:water (2:1)solvent 0.5 N in hydrochloric acid for about seventy hours at ambienttemperatures.

The novel compounds of this invention represented by formula (CXXXIV)and related compounds are particularly interesting sunce they represent"stabilized" prostaglandin A types, which cannot rearrange to thebiologically relatively inactive prostaglandins of the B series.

Utilization of Grignard (XLII) (see Flowsheet F, hereinabove) in thesequence of Flowsheet P provides the compounds of (CXXX) wherein C₁₃-C₁₄ is ethylene. Provided there are no other double bonds in themolecule these substances can also be obtained by catalytichydrogenation of the compounds represented by formula (CXXXV).

The alkylation process described above for Flowsheets O and P also givesthe corresponding 8α-alkyl derivatives which are separable from the8β-alkyl isomer by chromatography. Thus, for example, in Flowsheet Otreatment of enolate (CXXV) with R'₇ I gives not only the 8β-alkylproduct (CXXVI) as shown, but there also is obtained the 8α-alkylderivative (CXXXVI) shown below. In Flowsheet P, alkylation of enolate(CXXXII) also provides, in addition to (CXXXIII) shown, the8α-alkyl-8-iso product (CXXXVII), shown below. These 8α-alkyl-8-isoderivatives can be deblocked and carried through the same series oftransformation shown for the 8β-derivatives (CXXVI) and (CXXXIII) inFlowsheets O and P, respectively. These novel 8α-alkyl-8-iso derivativesand their transformation products are also a part of this invention, asare the key intermediate enolates represented by structures (CXXV) and(CXXXII). ##STR36##

The novel compounds of the present invention have potential utility ashypotensive agents, anti-ulcer agents, agents for the treatment ofgastric hypersecretion and gastric erosion, bronchodilators,antimicrobial agents, anticonvulsants, abortifacients, agents for theinduction of labor, agents for the induction of menses,fertility-controlling agents, central nervous system regulatory agents,analgesic agents, salt and water-retention regulatory agents, diuretics,fat metabolic regulatory agents, serum-cholesterol lowering agents,anti-infammatory agents and as agents for the inhibition of plateletaggragation, and for the treatment of periodontal disease, glaucoma,uveitis, sickle cell anemia and psoriasis. Certain of the novelcompounds of this invention possess utility as intermediates for thepreparation of other of the novel compounds of this invention.

The compounds of this invention provide protection against theulcerogenic properties of indomethacin. This assay was carried out inthe following manner.

Rats were starved for 48 hours (water was given ad libitum).Indomethacin (20 mg./kg. of body weight) was administered by thesubutaneous route and one-half the dose of the test compound wasadministered by gavage at the same time. After three hours, the secondhalf of the test compound was administered also by Gavage. Five hoursafter the administration of indomethacin the animals were decapitatedand the stomachs removed. The stomachs were washed with distilled water,blotted on gauze, cut along the larger curvature, and the contentsrinsed with distilled water. The stomachs were spread out, pinned on acork and visualized under magnifying glass for ulcers. The criteria forscoring of ulcers was as previously reported. [Abdel-Galil et al. Brit.J. Pharmac. Chemotherapy 33:1-14 (1968)].

    ______________________________________                                        Score                                                                         ______________________________________                                        0          Normal stomach                                                     1          Petechial hemorrhage or pin point ulcer                            2          1 or 2 small ulcers                                                3          Many ulcers, a few large                                           4          Many ulcers, mainly large                                          ______________________________________                                    

Control animals treated with indomethacin but not test compoundconsistently give scores of about 3.0-3.5. Control animals treated withneither indomethacin nor test compound give scores of about 0.5-0.8. Theresults obtained in this assay with typical compounds of the presentinvention are set forth in Table 1 below. Compounds producing a score of2.5 or lower are considered to be active.

                  TABLE I                                                         ______________________________________                                                   Total Oral                                                                    dose; mg./kg.                                                                 of body   Score                                                    Compound     weight      Treated  Control                                     ______________________________________                                        9-oxo-15-hydroxy-                                                                          25          1.7      3.2                                         16-ethyl-13-trans-                                                            prostenoic acid                                                               9-oxo-15-hydroxy-                                                                          100         1.3      3.0                                         13-cis-prostenoic                                                             acid                                                                          9-oxo-15-hydroxy-                                                                          50          2.2      3.0                                         2-ethyl-13-trans-                                                             prostenoic acid                                                               9-oxo-8β-methyl-                                                                      12.5        2.0      3.0                                         15-hydroxy-13-                                                                trans-prostenoic                                                              acid                                                                          9-oxo-3-thia-15-                                                                           25          1.8      3.2                                         hydroxy-13-trans-                                                             prostenoic acid                                                               9-oxo-3-thin-15-                                                                           25          2.3      3.2                                         epi-hydroxy-13-                                                               trans-prostenoic                                                              acid                                                                          ______________________________________                                    

The novel compounds of the present invention are also effectiveinhibitors of gastric acid secretion and of ulcer development inexperimental animals, and thus are potentially valuable as agents forthe control of gastric acid secretion and of gastric erosion and asanti-ulcer agents. Gastric acid secretion inhibitory action is usuallymeasured by the "Shay rat" procedure.sup.(1,2) with some modificationsas follows.

The rats (male, CFE strain), were starved for 48 hours (water was givenad libitum) to permit evacuation of stomach contents. On the morning ofthe experiment, under ether anesthesia, the abdominal region was shavedand a midline incision (1-11/2") was made with a scapel. With the helpof a closed curved hemostate the duodenum was picked up. Upon gettingthe duodenum into view, fingers were used to pull the stomach throughthe opening, the stomach was then gently manipulated with fingers to ridthe stomach of air and residual matter which were pushed through thepylorus. Two-5 inch sutures were drawn under the pyloric-duodenalpuncture. A ligature, at the juncture was formed with one of thethreads. The second ligature was also formed but not tightened.

The test compound or the vehicle, usually 1 ml./mg. body weight, wereinjected into the duodenum as close as possible to the first ligature.After injection the second ligature was tightened below the injectionsite to minimize leakage. The stomach was placed back through theopening into the abdominal cavity, the area of incision was washed withsaline and the incision was closed with autoclips. (Occasionally,instead of an intraduodenal injection, animals were dosed by the oral orsubcutaneous route. In the latter case, dosing was done thirty to sixtyminutes before the operation).

Three hours later, the rats were decapitated and exanguinated, takingcare that blood did not drain into the estophagus. The abdominal cavitywas exposed by cutting with scissors and the esophagus close to thestomach was clamped off with a hemostat, the stomach was removed bycutting above the hemostat (the esophagus was cut) and between the twosutures. Extraneous tissue was removed, the stomach washed with salineand blotted on gauze. A slit was carefully made in the stomach which washeld over a funnel and the contents were collected in a centrifuge tube.The stomach was further cut along the outside edge and turned insideout. Two ml. H₂ O were used to wash the stomach contents into therespective centrifuged tube. The combined stomach contents and wash werethen centrifuged out for 20 minutes in the International Size 2Centrifuge (setting at 30). The supernatant was collected, volumemeasured and recorded, 2 drops of a phenolphthalein indicator (1% in 95%ethanol) were added and the solution was titrated with 0.02 N NaOH (orwith 0.04 N NaOH when large volumes of stomach contents wereencountered) to pH 8.4 (because of usual coloring of the stomachcontents, phenolphthalein was only used to permit visual indication thatthe end point was near) and the amount of acid present was calculated.

Compounds inducing inhibition of gastric acid secretion of 20% or morewere considered active. In a representative operation, and merely by wayof illustration, the results obtained with this assay with a typicalcompound of the present invention are given in Table 2, below.

                  TABLE 2                                                         ______________________________________                                                        Intraduodenal                                                                 dose, mg./kg.                                                                             Percent                                           Compound        of body weight                                                                            Inhibition                                        ______________________________________                                        9-oxo-15-hydroxy-                                                                             100         51                                                3,3-dimethyl-13-                                                              trans-prostenoic                                                              acid                                                                          ______________________________________                                    

Bronchodilator activity was determined in guinea pigs againstbronchospasms elicited by intravenous injections of 5-hydroxytryptamine,histamine or acetylcholine by the Konzett procedure. [See J. Lulling, P.Lievens, F. El Sayed and J. Prignot, Arzeimittel-Forschung, 18 995(1968).]

In the Table which follows bronchodilator activity for representativecompounds of this invention against one or more of the three spasmogenicagents is expressed as an ED₅₀ determined from the results obtained withthree logarithemic cumulative intravenous doses.

                  TABLE 2A                                                        ______________________________________                                        Bronchodilator Activity (Konzett Assays)                                      ED.sub.50 , mg./kg.                                                                   Spasmogenic Agent                                                               5-hydroxy-                                                          Compound  tryptamine   histamine  choline                                     ______________________________________                                        9-oxo-15-hy-                                                                            --           81.3 × 10.sup.-6                                                                   --                                          droxy-16-ethyl-                                                               13-trans-pro-                                                                 stenoic acid                                                                  9-oxo-15-hy-                                                                             106 × 10.sup.-6                                                                     81.3 × 10.sup.-6                                                                   320 × 10.sup.-6                       droxy-13-cis-                                                                 prostenoic                                                                    acid                                                                          9-oxo-15-hy-                                                                             329 × 10.sup.-6                                                                      145 × 10.sup.-6                                                                   533 × 10.sup.-6                       droxy-2-ethyl-                                                                13-trans-pro-                                                                 stenoic acid                                                                  9-oxo-15-hy-                                                                            50.8 × 10.sup.-6                                                                     92.6 × 10.sup.-6                                                                   320 × 10.sup.-6                       droxy-16-pro-                                                                 stynoic acid                                                                  ______________________________________                                    

This invention will be described in greater detail in conjunction withthe following specific examples. In these examples it is to be notedthat Example 724 follows directly after Example 699.

In the examples which follow reference to 15-hydroxy or 15-oxyderivatives, unless otherwise indicated is inclusive of both the 15-epiand 15 -normal racemates. In addition, all possible antipodes resultingfrom asymetry at C₈, C₁₂ and elsewhere in the prostenoic acid moleculeare included.

EXAMPLE 1 Preparation of2-carbalkoxy(methyl/ethyl)-2-(4-carbethoxybutyl)cyclopentan-1-one

To a stirred solution of the sodium cyclopentanone carboxylate enolatein dimethoxyethane, prepared from 187 g. (1.248 moles) of2-cyclopentanone carboxylate (mixed methyl and ethyl esters), 52.4 g.(1.248 moles) sodium hydride (57.2% in mineral oil) and 1.6 l. ofdimethoxyethane, is added dropwise 309 g. (1.212 moles) of ethyl5-iodovalerate. The reaction mixture is stirred and heated at reflux for18 hours. The mixture is cooled and filtered. The solvent is removedfrom the filtrate by evaporation and the residue is poured into dilutehydrochloric acid and extracted with ether. The combined extracts arewashed with water and saline, dried over magnesium sulfate andevaporated to given an oil. The oil is distilled under reduced pressureto give 274 g. of a light yellow oil, b.p. 140°-143° C. (0.17 mm).

EXAMPLE 2 Preparation of 2-(4-carboxybutyl)cyclopentan-1-one

A stirred mixture of 274 g of 2-carbalkoxy(mixed methyl and ethylesters)-2-(4-carbethoxybutyl)cyclopentan-1-one (Example 1), 600 ml. of20% hydrochloric acid and 325 ml. of acetic acid is heated at reflux for20 hours. Solution occurs in approximately 1/2 hour. The solution iscooled and diluted with water and extracted with ether. The combinedextracts are washed with saline and dried over magnesium sulfate andevaporated. The residue is evaporated twice with toluene to give 144 g.of an oil.

EXAMPLE 3 Preparation of 2-(4-carbethoxybutyl)cyclopentan-1-one

A stirred solution of 124 g. (0.673 mol) of2-(4-carboxybutyl)cyclopentan-1-one (Example 2), 800 ml. of ethanol and1 g. of p-toluenesulfonic acid monohydrate is heated at reflux for 18hours. The solvent is evaporated and the residue is dissolved in ether.The ether solution is washed with saline, dilute sodium bicarbonatesolution and again with saline, dried over magnesium sulfate andevaporated. The oil is distilled under reduced pressure to give 149 g.of a colorles oil, b.p. 106°-109° C. (0.23 mm).

EXAMPLE 4 Preparation of2-carbalkoxy(methyl/ethyl)-2-(3-carbethoxypropyl)cyclopentan-1-one

In the manner described in Example 1, treatment of 2-cyclopentanonecarboxylate (mixed methyl and ethyl esters) with sodium hydride indimethoxyethane followed by ethyl 4-iodobutyrate gives a yellow oil,b.p. 136°-137° C. (0.16 mm).

EXAMPLE 5 Preparation of 2-(3-carboxypropyl)cyclopentan-1-one

In the manner described in Example 2, treatment of 2-carbalkoxy(mixedmethyl and ethyl esters)-2-(3-carbethoxypropyl)cyclopentan-1-one(Example 4) with a 20% hydrochloric acid and acetic acid mixture gives ayellow oil.

EXAMPLE 6 Preparation of 2-(3-carbethoxypropyl)cyclopentan-1-one

In the manner described in Example 3, treatment of2-(3-carboxypropyl)cyclopentan-1-one (Example 5) with p-toluenesulfonicacid monohydrate in ethanol gives a colorless oil, b.p. 93° C. (0.10mm).

EXAMPLE 7 Preparation of ethyl and methyl2-(6-carbethoxyhexyl-1-cyclo-pentanon-2-carboxylate

In the manner described in Example 1, ethyl and methyl 2-cyclopentanonecarboxylate is reacted with ethyl 7-bromoheptanoate to furnish thesubject product, b.p. 147° C. (0.09 mm).

EXAMPLE 8 Preparation of 2-(6-carboxyhexyl)cyclopentan-1-one

In the manner described in Example 2, ethyl and methyl2-(6-carbethoxyhexyl)-1-cyclopentanone-2-carboxylate (Example 7) ishydrolyzed to furnish the subject product, b.p. 143° C. (0.05 mm).

EXAMPLE 9 Preparation of 2-(6-carbethoxyhexyl)cyclopentan-1-one

In the manner described in Example 3,2-(6-carboxyhexyl)cyclopentan-1-one (Example 8) is esterified to furnishthe subject product, b.p. 110° C. (0.03 mm).

EXAMPLE 10 Preparation of 1-acetoxy-2-(6-carbethoxyhexyl)cyclopent-1-ene

A stirred solution of 100 g. of 2-(6-carbethoxyhexyl)cyclopentan-1-one(Example 9) in 250 ml of acetic anhydride containing 0.940 g. ofp-toluenesulfonic acid monohydrate is heated to boiling under partialreflux allowing distillate at 118° C. or less (i.e., acetic acid) toescape through a Vigreaux column equipped with a condenser to collectthe distillate. After 16 hours, during which period active anhydride isadded in portions in order to keep the solvent level at at least 100ml., the solution is cooled and poured cautiously into a stirred coldmixture of saturated sodium bicarbonate solution (400 ml.) and hexane(250 ml.). The resulting mixture is stirred for an additional 30 minutesduring which period solid sodium bicarbonate is added periodically toinsure a basic solution. The hexane layer is separated and washed withsaturated sodium chloride solution, dried with anhydrous magnesiumsulfate and taken to dryness. Distillation of the residual oil gives 102g. (87%) of pale yellow oil, b.p. 118° C. (0.07 mm).

EXAMPLE 11 Preparation of1-acetoxy-2-(3-carbethoxypropyl)cyclopent-1-ene

In the manner described in Example 10, treatment of2-(3-carbethoxypropyl)cyclopentan-1-one (Example 6) with aceticanhydride and p-toluenesulfonic acid monohydrate gives a yellow oil,b.p. 98°-103° C. (0.35 mm).

EXAMPLE 12 Preparation of 1-acetoxy-2-(4-carbethoxybutyl)cyclopent-1-ene

In the manner described in Example 10, treatment of2-(4-carbethoxybutyl)cyclopentan-1-one (Example 3) with acetic anhydrideand p-toluenesulfonic acid monohydrate gives a yellow oil, b.p.109°-110° C. (0.37 mm).

EXAMPLE 13 Preparation of 2-(6-carbethoxyhexyl)cyclopent-2-en-1-one

To a rapidly stirred mixture of 50 g. of1-acetoxy-2-(6-carbethoxyhexyl)cyclopent-1-ene (Example 10) in 150 ml.of chloroform, 200 ml. of water and 18.8 g. of calcium carbonate, cooledin an ice bath, is added dropwise over a period of about 30 minutes, asolution of 30 g. of bromine in 50 ml. of carbon tetrachloride. Afterstirring for an additional 45 minutes the chloroform layer is separatedand washed successively with dilute sodium thiosulfate solution,saturated sodium chloride solution, dried with anhydrous magnesiumsulfate and taken to dryness under reduced pressure.

The residual oil is dissolved in 50 ml. of N,N-dimethylformamide andadded to a mixture of 33 g. of lithium bromide and 32 g. of lithiumcarbonate in 375 ml. of N,N-dimethylformamide, previously dried byrefluxing with 375 ml. of benzene under a Dean-Stark apparatus followedby distillation of the benzene. The mixture is stirred at the refluxtemperature for 30 minutes, then cooled and poured into 850 ml. ofice-cold water. The resulting mixture is acidified (cautiously) with 4 Nhydrochloric acid and extracted with ether three times. The combinedether extracts are washed with saturated sodium chloride solution, driedwith anhydrous magnesium sulfate and taken to dryness under reducedpressure to afford 41.5 g. of an amber oil. In order to convert anyisomeric material to the desired product, 41.5 g. of the above materialis treated with 0.500 g. of p-toluenesulfonic acid monohydrate in 450ml. of absolute alcohol at the reflux temperature for 18 hours. Thesolution is taken to dryness under reduced pressure. The resulting gumis dissolved in ether and washed with saturated sodium bicarbonatesolution, saturated sodium chloride solution, dried with anhydrousmagnesium sulfate and taken to dryness under reduced pressure. Theresidual oil is distilled to give 30.2 g. of product; b.p. 118° C. (0.05mm); λ_(max) ^(MeOH) 229 mμ (ε9950): λ_(max) 5.75, 5.85, 6.15, 8.45 μ;vapor phase chromatography shows 99% product, containing 1%2-(6-carbethoxyhexyl)cyclopentan-1-one.

This product can be purified by the following procedure. A mixture of120 g. of 2-(6-carbethoxyhexyl)-2-cyclopentenone, containingapproximately 5% of the saturated analogue, and 7.67 g. (10 molepercent) of p-carboxyphenylhydrazine in 400 ml. of absolute ethanol isstirred at ambient temperature for 18 hours and is then refluxed for 1hour. The mixture is cooled, the solvent is evaporated, and the residueis taken up into 150 ml. of chloroform and passed through a column of450 g. of aluminum oxide (Merck). The filtrate is evaporated to yield acolorless oil containing <0.5% of the saturated impurity.

EXAMPLE 14 Preparation of 2-(3-carbethoxypropyl)cyclopent-2-en-1-one

In the manner described in Example 13, bromination of1-acetoxy-2-(3-carbethoxypropyl)cyclopent-1-ene (Example 11) followed bydehydrobromination with lithium bromide and lithium carbonate isproductive of the subject compound.

EXAMPLE 15 Preparation of 2-(4-carbethoxybutyl)cyclopent-2-en-1-one

In the manner described in Example 13, treatment of1-acetoxy-2-(4-carbethoxybutyl)cyclopent-1-ene (Example 12) with bromineand subsequent treatment of the brominated product with a mixture oflithium bromide and lithium carbonate in N,N-dimethylformamide isproductive of the subject compound. Treatment of this product withp-carboxyphenylhydrazine by the procedure of Example 13 furnishes aproduct which contains less than 0.5% of the corresponding saturatedketone.

EXAMPLE 16 Preparation of1-methoximino-2-(6-carbethoxyhexyl)-2-cyclopentene

To a mixture of 35.97 g. (0.151 mole) of2-(6-carbethoxyhexyl)-2-cyclopentenone (Example 13) and 15.0 g. (0.180mole) of methoxyamine hydrochloride in 300 ml. of absolute ethanol isadded 25 ml. of pyridine and the resulting solution is stirred for 20hours at ambient temperatures. The solvent is evaporated and the residueis partitioned between water and diethyl ether. The organic phase iswashed with water and saturated brine, dried (Na₂ SO₄), and the solventis evaporated to yield an oil. Distillation yields 38.7 g. of acolorless oil, b.p. 115°-118° C. (0.075 mm). IR (film): 1740, 1627,1053, 890 cm⁻¹. λ_(max) (MeOH) 243 (13,000). NMR δ(CDCl₃): 3.89.

EXAMPLE 17 Preparation of1-methoximino-2-(7-hydroxyheptyl)-2-cyclopentene

To an ice cooled solution of 34.10 g. (0.128 mole) of1-methoximino-2-(6-carbethoxyhexyl)-2-cyclopentene (Example 16) in 200ml. of benzene under nitrogen is added dropwise 225 ml. of a 25%solution of diisobutyl aluminum hydride in hexane. The resultingsolution is stirred for 2 hours at 0°-5° C., poured onto ice and dilutehydrochloric acid, and the aqueous phase is saturated with sodiumchloride. The organic phase is separated, washed with saturated brine,dried (Na₂ SO₄), and evaporated to yield an oil. The latter is dissolvedin 100 ml. of hot hexane and cooled to yield 24.3 g. of crystals, m.p.62°-64° C. IR (KBr) 3260, 1630, 1059, 893 cm⁻¹. λ_(max) 243 (14,200).NMR (CDCl₃)δ: 2.37.

EXAMPLE 18 Preparation of1-methoxyimino-2-(7-p-toluenesulfonyloxyhepty)-2-cyclopentene

To a solution of 5.00 g. (0.0222 mole) of1-methoximino-2-(7-hydroxyheptyl)-2-cyclopentene (Example 17) in 50 ml.of dry pyridine at 0° C. is added 8.45 g. (0.0444 mole) ofp-toluenesulfonyl chloride and the resulting solution is chilled at 5°C. overnight. The mixture is partitioned between 300 ml. of ice waterand diethyl ether. The organic phase is washed with 1:1 ice coldhydrochloric acid, cold water, and cold saturated brine, dried (NaSO₄/K₂ CO₃), and evaporated under reduced pressure at room temperature toyield an oil. The latter is dissolved in 600 ml. of hexane, treated with0.5 g. of Darco, filtered and evaporated to yield 7.7 g. of a colorlessoil. IR (film) 1600, 1192, 1182, 1053, 890 cm⁻¹. λ_(max) (MeOH) 228 and243.

EXAMPLE 19 Preparation of1-methoximino-2-(8,8-dicarbethoxyoctyl)-2-cyclopentene

To an alcoholic solution of sodiodiethyl malonate, prepared from 0.847g. (0.0368 g. atoms) of sodium, 100 ml. of absolute ethanol, and 7.05 g.(0.0440 mole) of diethyl malonate is added 7.7 g. of the tosylate ofExample 18 and the mixture is refluxed for 2 hours under a nitrogenatmosphere. The mixture is partitioned between cold dilute hydrochloricacid and diethyl ether, and the organic phase is washed with water andsaturated brine, dried (Na₂ SO₄), and evaporated to yield an oil. Theexcess diethyl malonate is distilled off under reduced pressure to yield6.45 g. of a yellowish oil. IR (film) 1755, 1728, 1625, 1054, 890 cm⁻¹.

EXAMPLE 20 Preparation of1-methoximine-2-(8,8-dicarboxyoctyl)-2-cyclopentene

A mixture of 6.45 g. of the diester of Example 19 and 6.72 g. ofpotassium hydroxide in 150 ml. of 1:1 aqueous methano is refluxed for 1hour, cooled, and is partitioned between water and diethyl ether. Theaqueous phase is acidified with hydrochloric acid, extracted with ether,and the organic phase is washed with water and saturated brine, dried(Na₂ SO₄) and evaporated to yield a solid. The solid is crystallizedfrom benzene to yield 4.15 g. of tan crystals, m.p. 135°-137° C.(--CO₂).

EXAMPLE 21 Preparation of1-methoximino-2-(8-carboxyoctyl)-2-cyclopentene

A solution of 3.926 g. (0.0126 mole) of the diacid of Example 20 in 20ml. of xylene is refluxed for 1.5 hours, cooled, and evaporated to yielda tan solid. IR (KBr) 1720, 1618, 1179, 1050, 986 cm⁻¹.

EXAMPLE 22 Preparation of 2-(8-carboxyoctyl)cycopent-2-en-1-one

The acid methoxime from Example 21 is refluxed for 5 hours with 55 ml.of acetone and 20 ml. of 2 N hydrochloric acid. The mixture is cooled,the solvent is evaporated, and the residue is partitioned between waterand diethyl ether. The organic phase is washed with water and saturatedbrine, dried (Na₂ SO₄), and evaporated to yield a tan solid. IR (KBr)1745, 1665 cm⁻¹. λ_(max) (MeOH) 228 (12,600).

EXAMPLE 23 Preparation of 2-(8-carbethoxyoctyl)cyclopent-2-en-1-one

The acid ketone from Example 22 is Fisher esterified with 100 ml. ofabsolute ethanol, 100 ml. of benzene, and 20 mg. of p-toluenesulfonicacid for 6 hours, cooled, and the solvent is evaporated. The resultingoil is dissolved in 3:1 benzene-ether and the solution is passed througha column of 100 g. of Florisil®. The filtrate is evaporated and theresidue is distilled to yield 2.97 g. of a colorless oil, b.p. 137°-139°C. (0.05 Torr).

EXAMPLE 24 Preparation of 2-(4-carbethoxybutyl)-2-cyclopentenonemethoxime

Treatment of 2-(4-carbethoxybutyl)-2-cyclopentenene (Example 15) withmethoxyamine hydrochloride in the manner described in Example 16 givesan oil, b.p. 107°-109° C. (0.05 mm). IR (film): 1740, 1628, 1050, 885cm⁻¹. λ_(max) (MeOH) 243 (13,600).

EXAMPLE 25 Preparation of 2-(5-hydroxypentyl)-2-cyclopentenone methoxime

Treatment of 2-(4-carbethoxybutyl)-2-cyclopentenomethoxime (Example 24)with diisobutyl aluminum hydride in the manner described in Example 17gives crystals, m.p. 33°-35° C. IR (KBr) 3420, 1630, 1050, 886 cm⁻¹.λ_(max) ^(MeOH) 243 (12,020).

EXAMPLE 26 Preparation of2-(5-p-toluenesulfonyloxypentyl)-2-cyclopentenone methoxime

Treatment of 2-(5-hydroxypentyl)-2-cyclopentenone methoxime (Example 25)with p-toluenesulfonyl chloride in pyridine in the manner described inExample 18 gives a colorless oil. IR (film) 1600, 1190, 1180, 1050, 885cm⁻¹.

EXAMPLE 27 Preparation of 2-(6,6-dicarbethoxyoctyl)-2-cyclopentenemethoxime

To a solution of sodio diethyl ethylmalonate, prepared from 1.63 g.(0.0387 mole) of sodium hydride in mineral oil (57.2%), 100 ml. ofethylene glycol dimethyl ether and 8.5 g. (0.0452 mole) of ethyl diethylmalonate, is added 7.5 g. of tosylate from Example 26 in 20 ml. ofethylene glycol dimethyl ether and the mixture is refluxed for 3 hoursand then allowed to stand at room temperature for 18 hours undernitrogen atmosphere. The reaction mixture is filtered and most of thesolvent is removed. The mixture is partitioned between cold dilutehydrochloric acid and diethyl ether, and the organic phase is washedwith water and saturated brine, dried (MgSO₄), and evaporated to yieldan oil. The excess ethyl diethyl malonate is distilled off under reducedpressure to yield 6.7 g. of a yellow oil. IR (film) 1755, 1728, 1627,1050, 885 cm⁻¹.

EXAMPLE 28 Preparation of 2-(6,6-dicarboxyoctyl)-2-cyclopentenonomethoxime

Treatment of 2-(6,6-dicarbethoxyoctyl)-2-cyclopenteno methoxime (Example26) with potassium hydroxide, and 1:1 aqueous methanol in the mannerdescribed in Example 20 gives a light yellow oil.

EXAMPLE 29 Preparation of 2-(6-carboxyoctyl)-2-cyclopentenone methoxime

In the manner described in Example 21, treatment of2-(6,6-dicarboxyoctyl)-2-cyclopentenone methoxime (Example 28) withxylene at reflux for 18 hours gives a yellow oil.

EXAMPLE 30 Preparation of 2-(6-carboxyoctyl)-2-cyclopentenone

Treatment of 2-(6-carboxyoctyl)-2-cyclopentenone methoxime (Example 29)with acetone and 2 N hydrochloric acid in the manner described inExample 22 gives a light yellow oil.

EXAMPLE 31 Preparation of 2-(6-carbethoxyoctyl)-2-cyclopentenone

Treatment of 2-(6-carboxyoctyl)-2-cyclopentenone (Example 30) withthionyl chloride and then treatment of the acid chloride with ethanol inthe usual manner gives an amber oil. The oil is placed on amagnesia-silica gel column and eluted with 3:1 benzene:ether. Thesolvent is removed and the residue is distilled, b.p. 122° C. (0.06 mm).

EXAMPLE 32 Preparation of diethyl1,1-dimethyl-5-tetrahydropyranylpentylmalonate

To 486 mg. (0.02 g.-atoms) of magnesium in 5 ml. of toluene containingone molar equivalent of tetrahydrofuran per equivalent of magnesium andone percent iodine (calculated in weight of magnesium) is added dropwise3.86 g. (0.02 mole) of 4-chloro-1-tetrahydropyranyloxybutane over aperiod of one hour with stirring, under nitrogen at 70° C. The reactionmixture is stirred at 70° C. for four hours. This reagent is then addeddropwise to 3 g. (0.015 mole) of ethyl isopropylidenemalonate in 40 ml.of tetrahydrofuran containing 392 mg. of tetrakis[iodo(tri-n-butylphosphine)copper (I)] and stirred at room temperaturefor 2 hours. The reaction mixture is poured into cold dilutehydrochloric acid and extracted with ether. The ether extract is driedover magnesium sulfate and concentrated to give 5.92 g. of subjectproduct as an oil.

EXAMPLE 33 Preparation of diethyl 1,1-dimethyl-5-hydroxypentylmalonate

A solution of 3.5 g. (0.01 mole) of diethyl1,1-dimethyl-5-tetrahydrofuranyloxypentylmalonate in 70 ml. of ethanolcontaining 3 ml. of hydrochloric acid is allowed to stir at roomtemperature for 18 hours. The solution is concentrated, diluted withwater and extracted with ether. The ether extract is washed with water,dried over magnesium sulfate and concentrated to give 3.262 g. of alight yellow oil. The oil is purified by distillation, b.p. 116°-117° C.(0.05 mm).

EXAMPLE 34 Preparation of 3,3-dimethyl-7-hydroxyheptanoic acid

A mixture of 32 g. (0.117 mole) of diethyl1,1-dimethyl-5-hydroxypentylmalonate, 25 g. of potassium hydroxide and600 ml. of methanol-water (1:1) is heated at reflux for 8 hours and thenallowed to stand at room temperature for 18 hours. The methanol isremoved, diluted with water and the reaction mixture is acidified withconcentrated hydrochloric acid. The mixture is extracted with ether. Theextract is washed with water and saline, dried over anhydrous magnesiumsulfate and concentrated to give 27 g. of1,1-dimethyl-5-hydroxypentylmalonic acid. This crude oil is dissolved in200 ml. of bis-(2-methoxyethyl)ether and is heated at reflux for 4 hoursand then allowed to stand at room temperature overnight. The solvent isremoved and the reaction mixture is diluted with water and extractedwith ether. The organic solution is washed with saline, dried overmagnesium sulfate and concentrated to give 18 g. of product as an oil.

EXAMPLE 35 Preparation of ethyl 3,3-dimethyl-7-chloroheptanoate

To a solution of 3.484 g. (0.02 mole) of 3,3-dimethyl-7-hydroxyheptanoicacid in 25 ml. of chloroform containing 3 drops of dimethylformamide isadded 5.8 ml. (0.08 mole) of thionyl chloride and the solution is thenheated at reflux for 3-4 hours. The solution is concentrated to give theintermediate 3,3-dimethyl-7-chloro-1-heptanoyl chloride. The acidchloride is dissolved in a minimum amount of benzene and added slowly to20 ml. benzene, 10 ml. of ethanol and 2.65 ml. of collidine. Thesolution is heated at reflux for one hour and then concentrated. Theresidue is dissolved in ether, washed with water, dilute sodiumbicarbonate solution and saline. The organic solution is dried overmagnesium sulfate and concentrated to give 3.57 g. of product as ayellow oil.

EXAMPLE 36 Preparation of ethyl 3,3-dimethyl-7-iodoheptanoate

To a solution of 3.57 g. (0.0162 mole) of ethyl3,3-dimethyl-7-chloroheptanoate in 100 ml. of methyl ethyl ketone isadded 4 g. of sodium iodide and the mixture heated at reflux for 18hours. The reaction mixture is cooled, filtered and concentrated. Theresidue is partitioned between ether and water. The aqueous phase isextracted several times with ether. The extract is washed with sodiumbisulfate solution, water and saline. The organic solution is dried overmagnesium sulfate and concentrated to give 4.182 g. of a yellow oil. Thematerial is purified by distillation, b.p. 86°-87° C. (0.18 Torr).

EXAMPLE 37 Preparation of2-carbalkoxy(methyl/ethyl)-2-(6-carbethoxy-5,5-dimethylhexyl)cyclopentan-1-one

This compound is prepared by treatment of sodio cyclopentanonecarboxylate enolate with ethyl 3,3-dimethyl-7-iodoheptanoate by theprocedure described in Example 1.

EXAMPLE 38 Preparation of2-(6-carboxy-5,5-dimethylhexyl)cyclopentan-1-one

This compound is prepared by decarbalkoxylation of 2-carbalkoxy (mixedmethyl and ethylester)-2-(6-carbethoxy-5,5-dimethylhexyl)cyclopentan-1-one by theprocedure described in Example 2.

EXAMPLE 39 Preparation of2-(6-carbethoxy-5,5-dimethylhexyl)cyclopentan-1-one

Esterification of 2-(6-carboxy-5,5-dimethylhexyl)cyclopentan-1-one withethanol by the procedure described in Example 3 is productive of thesubject compound.

EXAMPLE 40 Preparation of1-acetoxy-2-(6-carbethoxy-5,5-dimethylhexyl)cyclopent-1-ene

This compound is prepared from2-(6-carbethoxy-5,5-dimethylhexyl)cyclopentan-1-one and acetic anhydrideby the process described in Example 10.

EXAMPLE 41 Preparation of2-(6-carbethoxy-5,5-dimethylhexyl)cyclopent-2-en-1-one

This compound is prepared from1-acetoxy-2-(6-carbethoxy-5,5-dimethylhexyl)cyclopent-1-ene viabromination and dehydrobromination according to the procedure describedin Example 13.

EXAMPLE 42 Preparation of2-(3-carbethoxypropyl)-1-methoximino-2-cyclopentene

In the manner described for the preparation of the compound of Example16, 2-(3-carbethoxypropyl)-1-methoximino-2-cyclopentene is prepared from2-(3-carbethoxypropyl)-2-cyclopentenone (Example 14) and methoxyaminehydrochloride.

EXAMPLE 43 Preparation of2-(4-hydroxybutyl)-1-methoximino-2-cyclopentene

In the manner described for the preparation of the compound of Example17, 2-(4-hydroxybutyl)-1-methoximino-2-cyclopentene is prepared from2-(3-carbethoxypropyl)-1-methoximino-2-cyclopentene anddiisobutylaluminum hydride.

EXAMPLE 44 Preparation of2-(6-carbethoxy-5-oxahexyl)-1-methoximino-2-cyclopentene

To an ice cold solution of 4.833 g. (0.0266 mole) of2-(4-hydroxypentane)-1-methoximino-2-cyclopentene in 50 ml. of drytetrahydrofuran under nitrogen is added 16.7 ml. of 1.6 molar n-butyllithium in hexane, dropwise. The reaction mixture is stirred for 0.5hour and then 4.85 g. (0.029 mole) of ethyl bromoacetate is addeddropwise. The reaction mixture is stirred overnight at room temperatureand then refluxed for 1.5 hours. The reaction is cooled and poured intowater and extracted several times with ether. The ether extracts arewashed with saline, dried over magnesium sulfate, and concentrated. Theresidue is placed on an alumina column, chloroform being used as a washsolvent. The combined washings are concentrated to dryness to give 4.903g. of product an a yellow oil.

EXAMPLE 45 Preparation of 2-(6-carboxy-5-oxahexyl)-2-cyclopentenone

In the manner described in Example 22, treatment of2-(6-carbethoxy-5-oxahexyl)-1-methoximino-2-cyclopentene with acetoneand 2 N hydrochloric acid at reflux gives the subject compound as ayellow oil.

EXAMPLE 46 Preparation of 2-(6-carbethoxy-5-oxahexyl)-2-cyclopentenone

In the manner described in Example 23, treatment of2-(6-carboxy-5-oxahexyl)-2-cyclopentenone with p-toluenesulfonic acid inethanol produces the subject product as a light yellow oil.

EXAMPLE 47 Preparation of2-(6-carboxy-5-oxahexyl)-1-methoximino-2-cyclopentenone

To an ice cold solution of 3.66 g. (0.02 mole) of2-(4-hydroxybutyl)-1-methoximino-2-cyclopentene (Example 43) in 50 ml.of 1,2-dimethoxyethane under nitrogen is added dropwise 17 ml. of 1.6 Mn-butyl lithium in hexane. The reaction mixture is stirred for half anhour and then the lithium salt of chloroacetic acid, prepared from 1.89g. (0.02 mole) of chloroacetic acid and 16 ml. of 1.6 M n-butyl lithiumin 20 ml. of dimethoxyethane, is added and the reaction mixture isheated at reflux for 48 hours. The solvent is evaporated and the residueis partitioned between ether and water. The aqueous phase is acidifiedwith hydrochloric acid and extracted with ether. The organic phase iswashed with water and saturated saline solution, dried (MgSO₄), andevaporated to give 3.35 g. of a yellow oil.

EXAMPLE 48 Preparation of 2-(6-carboxy-5-oxahexyl)-2-cyclopenten-1-one

In the manner described in Example 22, treatment of2-(6-carboxy-5-oxahexyl)-1-methoximino-2-cyclopentene (Example 47) withacetone and 2 N hydrochloric acid at reflux gives the subject compoundas a yellow oil.

EXAMPLE 49 Preparation of1-methoxyimino-2-(4-methanesulfonyloxybutyl)-2-cyclopentene

To a solution of 1.83 g. (0.01 mole) of1-methoximino-2-(4-hydroxybutyl)-2-cyclopentene (Example 43) in 10 ml.of methylene chloride containing 1.52 g. (0.015 mole) of triethylamineis added 1.265 g. (0.011 mole) of methanesulfonyl chloride over a periodof 5-10 minutes at -10°-0° C. Stirring is continued for 15 minutes andthe solution is then washed with cold water, cold 10% hydrochloric acid,cold sodium bicarbonate solution, and cold saline solution. The organicphase is dried (MgSO₄) and concentrated to give an oil which solidifiesupon cooling. Crystallization from ether-petroleum ether (30°-60° C.)gives 1.797 g. of white crystals, m.p. 67°-68° C.

EXAMPLE 50 Preparation of 1-methoximino-2-(5-cyanopentyl)-2-cyclopentene

A mixture of 2.75 g. (0.01 mole) of1-methoximino-2-(5-methanesulfonyloxypentyl)-2-cyclopentene (Example 60)and 1.47 g. (0.03 mole) of sodium cyanide in 20 ml. of dryN,N-dimethylformamide is heated at 65°-70° C. for 3 hours. The cooledreaction mixture is poured into water and extracted with diethyl ether.The organic phase is washed with water and saturated saline solution,dried (MgSO₄), and evaporated to give 1.89 g. of a light yellow oil.

EXAMPLE 51 Preparation of1-methoximino-2-(5-carboxypentyl)-2-cyclopentene

A mixture of 1.89 g. (0.0092 mole) of1-methoximino-2-(5-cyanopentyl)-2-cyclopentene (Example 50) and 1 g.(0.025 mole) of sodium hydroxide in 50 ml. of 1. l aqueous-ethanol isrefluxed for 48 hours, cooled, and partitioned between water and diethylether. The aqueous phase is acidified with hydrochloric acid, extractedwith diethyl ether, and the organic phase is washed with water andsaturated saline solution, dried (MgSO₄), and evaporated to give 1.86 g.of a yellow oil.

EXAMPLE 52 Preparation of 2-(5-carboxypentyl)-2-cyclopentenone

A solution of 1.86 g. (0.00825 mole)1-methoximino-2-(5-carboxypentyl)-2-cyclopentene (Example 51) in 44 ml.of acetone and 13.1 ml. of 2 N hydrochloric acid is refluxed for 5hours. The solvent is partially evaporated and a solid precipitates andis collected. The residue is extracted with diethyl ether and theorganic phase is washed with saturated saline solution, dried (MgSO₄),and evaporated to yield additional solid. The combined solid material iscrystallized from ether/pet ether (30°-60° C.°) to yield crystallinematerial, m.p. 70°-72° C.

EXAMPLE 53 Preparation of 2-(5-carbethoxypentyl)-2-cyclopentenone

A solution of 1.309 g. (0.00668 mole) of2-(5-carboxypentyl)-2-cyclopentenone (Example 52) and 90 mg. ofp-toluenesulfonic acid in 150 ml. of ethanol is refluxed for 18 hours.The solvent is evaporated and the residue is dissolved in ether. Theorganic phase is washed with water, sodium bicarbonate solution, andsaturated saline solution, dried (MgSO₄), and evaporated to give 1.371g. of a light yellow oil.

EXAMPLE 54 Preparation of2-(5-acetoxypentyl)-2-carbomethoxy/carbethoxy-cyclopentanone

A mixture of sodiocyclopentanone carboxylate, prepared from 1200 g. (8.0moles) of cyclopentanone carboxylate (methyl and ethyl esters) and 200g. (8.3 moles) of mineral oil free sodium hydride in 10 l. of1,2-dimethoxyethane, 1320 g. (8.0 moles) of 5-chloro-1-amyl acetate [M.E. Synerholm, Journ. Amer. Chem. Soc., 69, 2681 (1947)], and 1200 g.(8.0 moles) of sodium iodide is refluxed under nitrogen for 18 hours.The mixture is cooled, concentrated to 4 l. and partitioned betweendilute hydrochloric acid and diethyl ether. The organic phase is washedwith water and saturated brine, dried (MgSO₄), and evaporated to yield1920 g. of an oil.

EXAMPLE 55 Preparation of2-(5-hydroxypentyl)cyclopentanone/2-(5-acetoxypentyl)-cyclopentanone

A mixture of 4,500 g. (16.2 moles) of2-(5-acetoxypentyl)-2-carbomethoxy/carboethoxy-cyclopentanone (Example54), 2.2 l. of glacial acetic acid, 1 l. of concentrated hydrochloricacid, and 1 l. of water is refluxed for 18 hours, cooled, andpartitioned between saturated brine and benzene. The organic phase iswashed with saturated brine, dried (MgSO₄), and evaporated in vacuo toyield 3155 g. of an oil.

EXAMPLES 56 Preparation of 1-acetoxy-2-(5-acetoxypentyl)-1-cyclopentene

A solution of 400 g. (2.04 moles, of a mixture of2-(5-hydroxypentyl)cyclopentanone and 2-(5-acetoxypentyl)cyclopentanone(Example 55) and 4.0 g. of p-toluenesulfonic acid monohydrate in 1 l. ofacetic anhydride is refluxed at a rate to maintain a steady distillationof acetic acid from the reaction through a helix-packed fractionationcolumn. The reaction is continued with the addition of acetic anhydrideto maintain a constant volume until complete conversion of startingmaterials to product is evident. The mixture is cooled and partitionedbetween 2 l. of hexane and 3 l. of cold water containing solid sodiumbicarbonate to maintain a neutral pH. The organic phase is washed withsaturated brine, dried (MgSO₄), and evaporated to yield 452 g. of anoil.

EXAMPLE 57 Preparation of 2-(5-acetoxypentyl)-2-cyclopentenone

To a well stirred mixture of 405 g. (4.05 moles) of calcium carbonate, 3l. of water, and 2.5 l. of chloroform cooled to 5° C. is addedsimultaneously 1016 g. (4.0 moles) of1-acetoxy-2-(5-acetoxy-pentyl)-1-cyclopentene (Example 56) and asolution of 648 g. (4.05 moles) of bromine in 500 ml. of carbontetrachloride at a rate to maintain a temperature below 10° C. Themixture is stirred for half an hour after addition of the reagents andthe phases are then separated. The organic phase is washed with 2%sodium thiosulfate solution, water, and saturated brine, dried (MgSO₄),and evaporated in vacuo to an oil. The oil is immediately added to arefluxing slurry of 500 g. (5.0 moles) of calcium carbonate in 2.5 l ofN,N-dimethylacetamide under nitrogen and the mixture is then refluxedfor thirty minutes. The mixture is cooled, filtered, and partitionedbetween water and diethyl ether. The organic phase is washed with waterand saturated brine, dried (MgSO₄), and evaporated to yield 757 g. of anoil, b.p. 116°-118° C. (0.25 mm.)

EXAMPLE 58 Preparation of1-methoximino-2-(5-acetoxypentyl)-2-cyclopentene

In the manner described for Example 16,2-(5-acetoxypentyl)-2-cyclopentenone (Example 57) is treated withmethoxyamine hydrochloride in pyridine and ethanol to yield the subjectcompound, b.p. 101°-103° C. (0.20 mm.).

EXAMPLE 59 Preparation of1-methoximino-2-(5-hydroxpentyl)-2-cyclopentene

A mixture of 74 g. (0.22 mole) of1-methoximino-2-(5-acetoxypentyl)-2-cyclopentene (Example 58) and 56 g.(1.0 mole) of potassium hydroxide in 300 ml. of 1:1 aqueous methanol isrefluxed for 2 hours and then cooled. The solvent is partially removedin vacuo and the residue is partitioned between saturated brine anddiethyl ether. The organic phase is washed with saturated brine, dried(MgSO₄), and evaporated to yield an oil which crystallized, m.p. 35°-36°C.

EXAMPLE 60 Preparation of1-methoximino-2-(5-methanesulfonyloxypentyl)-2-cyclopentene

To a cold solution of 9.85 g. (0.05 mole) of1-methoximino-2-(5-hydroxypentyl)-2-cyclopentene (Example 59) and 7.6 g.(0.075 mole) of triethylamine in 100 ml. of methylene chloride at -10°C. is added 6.3 g. (0.055 mole) of methanesulfonyl chloride at a rate tomaintain a temperature of -10° to 0° C. The mixture is then stirred for15 minutes and then poured into ice water. The organic phase is washedwith cold 10% hydrochloric acid, cold saturated sodium bicarbonatesolution, and cold saturated brine, dried (MgSO₄), and evaporated toyield a solid, m.p. 78°-80° C.

EXAMPLE 61 Preparation of1-methoximino-2-(6,6-dicarbethoxyhexyl)-2-cyclopentene

To a suspension of a diodiethylmalonate in 1,2-dimethoxyethane, preparedfrom 248 g. (1.55 mole) of diethyl malonate and 17.2 g. (0.95 mole) ofmineral oil free sodium hydride in 1 l. of 1,2-dimethoxyethane undernitrogen, is added 170 g. (0.62 mole) of1-methoximino-2-(5-methanesulfonyloxypentyl)-2-cyclopentene (Example 60)in 1.5 l. of 1,2-dimethoxyethane and the mixture is refluxed for 5hours. The mixture is cooled, filtered, and the nolvent in evaporated.The residue is partitioned between cold dilute hydrochloric acid andwater, and the organic phase is washed with saturated brine, dried(MgSO₄), and evaporated to remove solvent and excess diethyl malonate toyield 209 g. of an oil.

EXAMPLE 62 Preparation of1-methoximino-2-(6,6-dicarboxyhexyl)-2-cyclopentene

In the manner described in Example 20,1-methoximino-2-(6,6-dicarbethoxyhexyl)-2-cyclopentene is treated withpotassium hydroxide in 1:1 aqueous methanol and then hydrochloric acidto yield the desired compound as crystals from diethyl ether, m.p.110°-115° C.

EXAMPLE 63 Preparation of1-methoximino-2-(6-carboxyhexyl)-2-cyclopentene

A solution of 141 g. (0.50 mole) of1-methoximino-2-(6,6-dicarboxyhexyl)-2-cyclopentene in 500 ml. ofbis-(2-methoxyethyl) ether is refluxed for 2 hours, cooled, andevaporated to yield an oil. The latter is crystallized from hexane toyield 92 g. of solid, m.p. 70°-72° C.

EXAMPLE 64 Preparation of 2-(6-carboxyhexyl)-2-cyclopentenone

In the manner described in Example 22, treatment of1-methoximino-2-(6-carboxyhexyl)-2-cyclopentene (Example 63) withacetone and 2 N hydrochloric acid at reflux provides the subjectcompound.

EXAMPLE 65 Preparation of 2-(6-carbethoxyhexyl)-2-cyclopentenone

Fischer estification of 2-(6-carboxyhexyl)-2-cyclopentenone (Example 64)in the manner of Example 23 provides the subject compound.

EXAMPLE 66 Preparation of1-methoximino-2-(6-fluoro-6,6-dicarbethoxyhexyl)-2-cyclopentene

To a solution of sodiodiethyl fluoromalonate, prepared from 2.062 g.(0.0491 mole) of sodium hydride in mineral oil (57.2%), 40 ml. of dryN,N-dimethylformanide and 8.174 g. (0.0458 mole) of diethylfluoromalonate is added dropwise 11.32 g. (0.0413 mole) of1-methoximino-2-(5-methylsulfonyloxypentyl)-2-cyclopentene (Example 60)in 60 ml. of N,N-dimethylformamide. The mixture is refluxed for 2 hoursunder a nitrogen atmosphere. The mixture is concentrated and partitionedbetween cold dilute hydrochloric acid and diethyl ether, and the organicphase is washed with saturated brine, dried (MgSO₄), and evaporated toyield 13.631 g. (92%) of a yellow oil.

EXAMPLE 67 Preparation of 1-methoximino-2-(6-fluoro,6,6-dicarboxyhexyl)-2-cyclopentene

A mixture of 13.631 g. of the diester of Example 66 and 16 g. ofpotassium hydroxide in 364 ml. of 1:1 aqueous methanol is refluxed for 5hours, cooled, concentrated, and is partitioned between water anddiethyl ether. The aqueous phase is acidified with hydrochloric acid,extracted with ether, and the organic phase is washed with saturatedbrine, dried (MgSO₄) and evaporated to yield a solid. The solid iscrystallized from diethyl ether petroleum ether (30°-60° C.) to give 10g. (90%) of white crystals, m.p. 143°-145° C. (--CO₂).

EXAMPLE 68 Preparation of1-methoximino-2-(6-fluoro-6-carboxyhexyl)-2-cyclopentene

A solution of 10 g. of the diacid of Example 67 in 60 ml. of2-methoxyethyl ether is refluxed for 7 hours, cooled, and evaporated toyield 8.5 g. (95%) of a tan solid. A sample is crystallized from diethylether-petroleum ether (30°-60° C.) to give white crystals, m.p. 98°-100°C.

EXAMPLE 69 Preparation of2-(6-fluoro-6-carboxyhexyl)cyclopent-2-en-1-one

The acid methoxime (8.5 g.) from Example 68 is refluxed for 5 hours with180 ml. of acetone and 64 ml. of 2 N hydrochloric acid. The mixture iscooled, the solvent is evaporated, and the residue is partitionedbetween water and diethyl ether. The organic phase is washed withsaturated brine, dried (MgSO₄) and evaporated to yield 7.4 g. (98%) of alight yellow oil.

EXAMPLE 70 Preparation of2-(6-fluoro-6-carbethoxyhexyl)cyclopent-2-en-1-one

The acid ketone (7.4 g.) from Example 69 is Fisher esterified with 300ml. of absolute ethanol and 400 mg. of p-toluenesulfonic acid for 18hours, cooled, and the solvent is evaporated. The resulting oil isdissolved in ether, washed with dilute sodium bicarbonate solution, andsaline, dried (MgSO₄), and evaporated to give 7.306 g. (86%) of a lightyellow oil.

EXAMPLE 71 Preparation of 2-(7-cyanoheptyl)-1-methoximino-2-cyclopentene

Treatment of 1-methoximino-2-(7-p-toluenesulfonyloxy)-2-cyclopentene(Example 18) with sodium cyanide in the manner of Example 50 isproductive of the subject compound.

EXAMPLE 72 Preparation of2-(7-carboxyheptyl)-1-methoximino-2-cyclopentene

Alkaline hydrolysis of 2-(7-cyanoheptyl)-1-methoximino-2-cyclopentene(Example 71) by the procedure of Example 51 is productive of the subjectcompound.

EXAMPLE 73 Preparation of 2-(7-carboxyheptyl)-2-cyclopenten-1-one

Hydrolysis of the methoxime of Example 72 with acetone-hydrochloric acidby the procedure of Example 52 is productive of the subject compound.

EXAMPLE 74 Preparation of 2-(7-carbethoxyheptyl)-2-cyclopenten-1-one

Fisher estification of the carboxylic acid of Example 73 by theprocedure of Example 53 in productive of the subject compound.

EXAMPLE 75 Preparation of2-(6,6-dicarbethoxy-6-phenylhexyl)-1-methoximino-2-cyclopentene

Treatment of 1-methoximino-2-(5-methanesulfonyloxypentyl)-2-cyclopentene(Example 60) with sodio diethyl phenylmalonate by the procedure ofExample 61 is productive of the subject compound.

EXAMPLE 76 Preparation of2-(6,6-dicarboxy-6-phenylhexyl)-1-metoxyimino-2-cyclopentene

Alkaline hydrolysis of2-(6,6-dicarbethoxy-6-phenylhexyl)-1-methoximino-2-cyclopentene (Example75) by the procedure of Example 20 is productive of the subject diacid.

EXAMPLE 77 Preparation of2-(6-carboxy-6-phenylhexyl)-1-methoximino-2-cyclopentene

Decarboxylation of2-(6,6-dicarboxy-6-phenylhexyl)-1-methoximino-2-cyclopentene (Example76) by the procedure of Example 63 is productive of the subjectcompound.

EXAMPLE 78 Preparation of2-(6-carboxy-6-phenylhexyl)-2-cyclopentene-1-one

Methoxime cleavage of2-(6-carboxy-6-phenylhexyl)-1-methoximino-2-cyclopentene (Example 77) inthe manner of Example 69 is productive of the subject ketone.

EXAMPLE 79 Preparation of2-(6-carbethoxy-6-phenylhexyl)-2-cyclopenten-1-one

Fisher esterification of the carboxylic acid of Example 78 in the mannerof Example 70 is productive of the subject keto-ester.

EXAMPLE 80 Preparation of2-(6-fluoro-6,6-dicarbethocyhexyl)-1-methoximino-2-cyclopentene

An ethanolic solution of sodium ethoxide, prepared from 0.389 g. ofsodium and 40 ml. of absolute ethanol, is treated at ambienttemperatures with 5.05 g. of2-(6,6-dicarbethoxyhexyl)-1-methoximino-2-cyclopentene (Example 61). Theresulting solution is cooled to -20° C. and then treated with a streamof perchloryl fluoride until the mixture becomes neutral. The excessperchloryl fluoride is removed with a stream of nitrogen and the mixtureis retreated with 10 ml. of an ethanol. solution of sodium ethoxide(from 0.350 g. of sodium) and then with perchloryl fluoride until themixture becomes neutral. The excess perchloryl fluoride is removed witha stream of nitrogen and the mixture is filtered and evaporated to anoil. The latter is partitioned between ether and water and the organicphase is washed with saturated saline, dried (Na₂ SO₄) and evaporated toafford the subject compound.

EXAMPLE 81 Preparation of 2-(6-carbo-n-butoxyhexyl)cyclopent-2-en-1-one

A solution of 50 g. of 2-(6-carboxyhexyl)cyclopent-2-en-1-one [Bagli etal., Tetrahedron Letters, No. 5, 465 (1966)] in 1400 ml. of n-butanolcontaining 2.7 g. of p-toluenesulfonic acid monohydrate is allowed tostand at room temperature in a stoppered flask for about 24 hours. Thesolution is taken to dryness. The residue is taken up in ether and theethereal solution is washed several times with saline solution, driedwith anhydrous magnesium sulfate, and taken to dryness to afford thesubject butyl ester.

EXAMPLES 82-84

Treatment of 2-(6-carboxyhexyl)cyclopent-2-en-1-one by the procedure ofExample 81 with the appropriate alcohol affords the esters of thefollowing table.

                  TABLE IV                                                        ______________________________________                                        Example                                                                              Alcohol    Product Ester                                               ______________________________________                                        82     isopropanol                                                                              2-(6-carboisopropoxyhexyl)cyclopent-2-                                        cn-1-one                                                    83     methanol   2-(6-carbomethoxyhexyl)cyclopent-2-en-                                        1-one                                                       84     1-hydroxy- 2-(6-carbo-n-decyloxyhexyl)cyclopent-2-                            n-decane   en-1-one                                                    ______________________________________                                    

EXAMPLE 85 Preparation of diethyl (5-chloro-1,1-dimethylpentyl)malonate

To magnesium (71 g. 2.92 moles) under 1 l. of ether containing a fewcrystals of iodine is added dropwise 1-chloro-4-bromobutane (500 g.,2.92 moles) over a period of 30 minutes with stirring under nitrogen.The reaction is maintained at a temperature of 0° C. to 5° C. byimmersing in an acctone-Dry Ice bath periodically. After stirring for 30minutes at room temperature, the solution is chilled to below 0° C. andis then transferred to a dropping funnel from which it is added dropwiseto diethyl isopropylidene malonate (440 g., 2.19 moles) [A. C. Cope andE. M. Hancock, J.A.C.S. 60, 2644 (1938)] dissolved in 1000 ml. of ethercontaining the tri(n-butyl)phosphine complex of copper (1) iodide (57g.) [G. B. Kaufman and L. A. Teter, Inorganic Synthesis, 7, 9(1963)] at-10° C. with stirring under nitrogen over a period of two hours. Afterstirring at room temperature for four hours, the reaction mixture ispoured into cold dilute hydrochloric acid and is extracted with ether.The combined ether extracts are washed with saline solution, dried overmagnesium sulfate, and concentrated in vacuo to give 700 g. of crudeamber oil, which is distilled under vacuum to yield two fractions: 212.4g. with b.p. at 110° C.-135° C. at 0.3 mm. and 100.0 g. with b.p. at135° C.-145° C. at 0.3 mm. The total yield is 312.4 g. (49%).

EXAMPLE 86 Preparation of 3.3-dimethyl-7-chloroheptanoic acid

A mixture containing diethyl 5-(5-chloro-1,1-dimethylpentyl)malonate(648 g., 2.22 moles) potassium hydroxide (460 g. and eight liters of 1:1isopropanol: water is stirred at room temperature overnight. Most of theisopropanol is distilled and the residue is diluted with water, and thencarefully acidified with conc. hydrochloric acid. The mixture isextracted with ether and the extracts are washed with water and saline,dried over magnesium sulfate and concentrated in vacuo to give 548 g. ofcrude oil. The oil is dissolved in three liters of diglyne which isheated under reflux for sixteen hours. About 2.7 l. of solvent isdistilled, and the remainder is diluted with water and extracted withether. The extracts are washed with saline, dried over magnesium sulfateand concentrated in vacuo to give 428 g. of crude oil (99%).

EXAMPLE 87 Preparation of ethyl 3,3-dimethyl-7-chloroheptanoate

To a solution of 3,3-dimethyl-7-chloroheptanoic acid (428 g., 2.21moles) in 3 l. of chloroform containing 3 ml. of N,N-dimethylformamideis added 500 ml. of thionyl chloride and the resulting solution istested under reflux for three hours. The reaction solution then isconcentrated in vacuo and the residual acid chloride is dissolved in aminimum amount of benzene and added slowly to a solution containing 1260ml. of 95% ethanol and 2520 ml. of benzene and 390 ml. of collidine.After heating under reflux for one hour, the solution is concentratedand the residue is dissolved in ether washed with water, dilute sodiumbicarbonate solution and saline solution, dried over magnesium sulfateand concentrated to give 415 g. of crude oil, which is distilled undervacuum to yield two fractions 46.6 g. boiling at 75° C. (0.3 mm.) and236.7 g. boiling at 75° C.-80° C. (0.3 mm). The total yield is 283.3 g.(60%) and the product is indicated to be 95% pure by g.l.c.

EXAMPLE 88 Preparation of methyl/ethyl2-(6-carbethoxy-5,5-dimethylhexyl) cyclopentanone-2-carboxylate

Sodium hydride (67 g., 1.55 moles) is placed in a three l. round-bottomflask and to this is added 1.1 liters of glyme from a dropping funnelunder nitrogen flow and with stirring. To the resulting grayish mixtureis added the 2-carbalkoxycyclopentanone (mixed methyl and ethyl esters)dropwise over a period of 45 minutes with nitrogen flow whilst thetemperature is maintained in the range of 40°-55°. Ethyl3,3-dimethyl-7-chloroheptanoate (283 g., 1.28 moles) and potassiumiodide (195 g., 1.32 moles) are added and the mixture is heated atreflux overnight. After most of the solvent is distilled, the residue ismade acidic with dilute hydrochloric acid and is then extracted withether. The ether extracts are washed with water and saline solution,dried over magnesium sulfate, and concentrated in vacuo to 500 g. ofcrude yellow oil, which is distilled to give 405 g. (94% yield) of oilwith b.p. 140°-180° (0.8 mm).

EXAMPLE 89 Preparation of 7-(2-Cyclopentanone)-3,3 dimethylheptanoicacid

Methyl/Ethyl 2-(6-carbethoxy-5,5-dimethylhexyl)cyclopentanone-2-carboxylate (200 g., 0.6 moles), glacial acetic acid(180 ml) and 240 ml. of diluted hydrochloric acid, prepared from 100 ml.of conc. hydrochloric acid and 300 ml. of water, are placed in a 2 l.flask, containing a reflux condenser and a magnetic stirrer. The mixturethen is stirred at reflux for 24 hours. The reaction mixture is cooled,1 l. of water is added and the mixture is extracted several times withbenzene. The organic extracts are combined, washed with saturated sodiumchloride solution, dried over magnesium sulfate, filtered andconcentrated to an oil (173.5 g.). The oil is rendered basic with sodiumhydroxide solution, extracted with benzene and made acidic withhydrochloric acid and reextracted with benzene several times. Thebenzene layers are combined and washed with water, saturated sodiumchloride solution, dried over magnesium sulfate, filtered andconcentrated to yield 109.8 g. (78%) of crude oil, which was usedwithout further purification in the next step.

EXAMPLE 90 Preparation of Ethyl7-(2-Cyclopentanone)-3,3-dimethylheptanoate

To a solution of 7-(2-cyclopentanone)-3,3-dimethylheptanoic acid (45 g.,0.22 mol.) in 285 ml. of chloroform containing three drops ofN,N-dimethylformamide is added dropwise 25 ml. of thionyl chloride. Thesolution is stirred at room temperature for twenty minutes, the solventis removed at reduced pressure and the residual acid chloride isdissolved in a minimum amount of benzene and added slowly to a solutioncontaining 115 ml. of ethanol, 230 ml. benzene and 30 ml. of collodine.This solution is heated under reflux for fifteen minutes and thenconcentrated. The residue is dissolved in ether, washed with water,diluted sodium bicarbonate solution and saline solution, dried overmagnesium sulfate and concentrated to give 51 g. of crude oil.Distillation gives 40 g. (67%) b.p. 135-145 (0.1 mm.) of oil.

EXAMPLE 91 Preparation of1-Acetoxy-2-(6-carbethoxy-5,5-dimethylhexyl)cyclopent-1-ene

A solution of ethyl 7-(2-cyclopentanone)-3,3-dimethylheptanoate (90 g.,0.336 mol.) and p-toluenesulfonic acid (0.94 g.) in 250 ml. of aceticanhydride is heated to boiling under partial reflux, allowing distillateat 118° or less (i.e. acetic acid) to escape thru a Vigreux columnequipped with a condenser to collect the distillate. After ten hours 130ml. of distillate is collected. Another 50 ml. of acetic anhydride isadded and the reaction is heated for five more hours; an additional 125ml. of acetic anhydride is added, the reaction is heated for seven morehours; finally another 50 ml. of acetic anhydride is added and heatingis continued for four more hours. The solution is cooled and poured(cautiously) into a cold (0°-5°) mixture of saturated aqueous sodiumbicarbonate (400 ml.) and hexane (250 ml.). The resulting cold mixtureis stirred for thirty minutes during which time portions of solid sodiumbicarbonate are added periodically until carbon dioxide evalutionceases. The hexane layer is separated and washed with saturated sodiumchloride solution until the washings are neutral, dried over magnesiumsulfate and treated with Darco decolorizing charcoal for clarificationand then evaporated to dryness leaving an amber colored oil (87.5 g.,84%).

EXAMPLE 92 Preparation of2-(6-Carboxy-5,5-dimethylhexyl)cyclopent-2-en-1-one

To a rapidly stirred mixture of1-acetoxy-2-(6-carbethoxy-5,5-dimethylhexyl)cyclopent-1-ene (35 g.,0.113 mole) chloroform (95 ml.), water (125 ml.) and calcium carbonate(11.8 g.) cooled in an ice-bath is added dropwise over a period ofthirty minutes a solution of bromine (18.8 g.) in carbon tetrachloride(31 ml.). After stirring in the cold for an additional 45 minutes theorange colored chloroform layer is separated and washed with dilutesodium bisulfite and saturated saline solution, dried over magnesiumsulfate and taken to dryness in vacuo (bath temperature: 35°-40°)leaving an amber colored oil. A slurry of 100 ml. ofN,N-dimethylacetamide and 16.5 g. of CaCO₃ is stirred and heated toreflux under nitrogen flow. The above dried oil is added from a droppingfunnel rapidly, maintaining reflux and nitrogen flow for thirty minutes.The cooled reaction mixture is filtered, and the precipitate is washedwith ether. The filtrate is poured into two liters ice-cold water and isextracted with ether. The combined extracts and washing in washed withwater, saturated saline, treated with decolorizing charcoal, filtered.The solvent evaporated in vacuo to give 24 g. (77%) of subject product.

EXAMPLE 93 Preparation of 4-bromo-2(6-carboxyhexyl)cyclopent-2-en-1-one

A stirred mixture of 35.9 g. (0.171 moles) of 2-(6-carboxyhexyl)cyclopent-2-en-1-one [Bagli et al., Tetrahedron Letters, No. 5, 465(1966)], 35.0 g. (0.197 moles) of N-bromosuccinimide, and 600 ml. ofcarbon tetrachloride is refluxed for 35 minutes. The mixture is cooledto 5° C. and filtered. The filtrate is washed with cold water, driedover magnesium sulfate, and taken to dryness to give an oil,λ_(max).^(MeOH) =225 mμ (8850); νmax.=1705 (carbonyl groups) and 1625.cm⁻¹ (olefin group).

EXAMPLE 94 Preparation of2-(6-carboxyhexyl)-4-hydroxy-cyclopent-2-en-1-one

To a stirred solution of 10.6 g. (ca. 34 mmoles) of crude4-bromo-2-(6-carboxyhexyl)cyclopent-2-en-1-one (Example 93) in 100 ml.of acetone and 65 ml. of water is added 8.80 g. (45.2 mmoles) of silverfluoborate during 2 minutes. The temperature is maintained at 25°-30° C.by external cooling. The mixture is stirred for 90 minutes, filtered,saturated with sodium chloride, and extracted with ether. The extract isextracted with half saturated sodium bicarbonate solutions. The basicsolutions is reacidified with dilute hydrochloric acid, saturated withsodium chloride, and extracted with ether. The extract is washed withwater and saturated sodium chloride solution, dried over magnesiumsulfate, and concentrated. The crude product is purified by partitionchromatography on Celite to give an oil; λ_(max).^(MeOH) =233 mμ.(7360); νmax.=3380 (hydroxyl groups), 1710 (carbonyl groups), and 1632cm⁻¹ (olefin group).

EXAMPLE 95 Preparation of4-tetrahydropyranyloxy-2-(6-tetrahydropyranylcarboxyhexyl)cylopent-2-en-1-one

To a stirred solution of 5.59 g. (24.6 mmoles) of4-hydroxy-2-(6-carboxyhexyl) cylopent-2-en-1-one (Example 94) and 20.7g. (246 mmoles) of dihydropyran in 100 ml. of methylene chloride at 20°C. is added 47 mg. (0.246 mmoles) of p-toluenesulfonic acid monohydratein one portion. The temperature is maintained at 20°-25° C. by coolingand is stirred for one hour at that temperature. The solution is dilutedwith 200 ml. of ether and poured into a mixture of 40 ml. of saturatedsodium bicarbonate solution, 40 ml. of saturated sodium chloridesolution, and 80 ml. of water. The phases are separated, and the aqueousphase is extracted with additional ether. The total extract is washedsuccessively with water and saturated sodium chloride solution, driedover potassium carbonate, and freed of volatile matter by concentrationat reduced pressure to give an oil, λ_(max).^(MeOH) =223 mu (9500);νmax. 1730 (ester carbonyl group), 1705 (ketone carbonyl group), and1030 cm⁻¹ (tetrahydropyranyloxy groups).

EXAMPLE 96 Preparation of 2-(6,6-dicarbethoxyheptyl)-2-cyclopentenonemethoxime

The subject compound is prepared from sodio diethyl methylmalonate and2-(5-methanesulfonyloxypentyl)-2-cyclopentenone methoxime (Example 60)by the procedure described in Example 61.

EXAMPLE 97 Preparation of 2-(6-carboxyheptyl)-2-cyclopentenone methoxime

Saponification of 2-(6,6-dicarbethoxyheptyl)-2-cyclopentenone methoxime(Example 96) with potassium hydroxide by the method of Example 20 isproductive of 2-(6,6-dicarboxyheptyl)-2-cyclopentenone methoxime,decarboxylation of which in the manner of Example 63 provides thesubject compound.

EXAMPLE 98 Preparation of 2-(6-carboxyheptyl)-2-cyclopentenone

Methoxime cleavage of 2-(6-carboxyheptyl)-2-cyclopentenone methoxime(Example 97) in the manner of Example 22 provides the subject ketone.

EXAMPLE 99 Preparation of 2-(6-carbethoxyheptyl)-2-cyclopentenone

Esterification with ethanol of the acid chloride derived from2-(6-carboxyheptyl)-2-cyclopentenone in the manner of Example 31 isproductive of the subject compound.

EXAMPLE 100 Preparation of ethyl (methyl)7-(2-carbethoxycyclohexan-1-on-2-yl)heptanoate

To a stirred suspension of 51 g. of sodium hydride (57% in mineral oil)in 675 ml. of dimethylformamide is added 200 g. of 2-cyclohexanonecarboxylate (60% ethyl--40% methyl esters) over a 1-5 hr. period withexternal cooling to maintain the temperature at 20°-25° C. The reactionmixture is stirred at ambient temperature for 15 minutes and heated to50° C. over 15 minutes. To the stirred mixture is added 300 g. of ethyl7-bromoheptanoate during a 10 minute period. The reaction mixture isstirred at 50°-60° C. for 4 hours, cooled, and poured into water. Theproduct is obtained by ether extraction. The extract is washedsuccessively with water and saturated sodium chloride, dried andevaporated to give a liquid which is purified by distillation, IR 1735cm⁻¹ (ester carbonyls) and 1710 cm⁻¹ (ketone carbonyl).

EXAMPLE 101 Preparation of 7-(cyclohexan- 1-on-2-yl)heptanoic acid

A stirred mixture of 380 g. of mixed methyl and ethyl esters of7-(2-carbethoxycyclohexan-1-on-2-yl)heptanoate (Example 10), 202 ml. ofconcentrated sulfuric acid, 970 ml. of glacial acetic acid, and 970 ml.of water is refluxed for 22.5 hours. The cooled reaction mixture istreated with 380 g. of sodium carbonate and 2 liters of water and isextracted with ether. Acidic material is partitioned from the etherextract with 1.0 M sodium carbonate. The aqueous phase is acidified withconcentrated hydrochloric acid and extracted with ether. The extract iswashed successively with water and saturated sodium chloride, dried, andevaporated to give an oil.

EXAMPLE 102 Preparation of ethyl 7-(cyclohexan-1-on-2-yl)heptanoate

A solution of 232 g. of 7-(cyclohexan-1-on-2-yl)heptanoic acid in 2500ml. of ethanol is refluxed for 4.5 hours with 3.8 g. ofp-toluenesulfonic acid monohydrate. The solution is diluted with 200 ml.of benzene, and boiling is continued for 2 hours as 200 ml. ofdistillate is removed. The volume of the solution is concentrated to 500ml. After dilution with 500 ml. of ether the solution is extracted witha solution prepared from 50 ml. of saturated sodium bicarbonate, 50 ml.of saturated sodium chloride, and 100 ml. of water. The extract iswashed with saturated sodium chloride, dried, and evaporated. Theproduct is purified by distillation to give a liquid, IR 1740 cm⁻¹(ester carbonyl) and 1715 cm⁻¹ (ketone carbonyl).

EXAMPLE 103 Preparation of2-carbalkoxy(methyl/ethyl)-2-(3-carbethoxypropyl)cyclohexan-1-one

The subject compound is prepared in the manner described in Example 10by treatment of 2-cyclohexanone carboxylate (mixed methyl and ethylesters) with sodium hydride and ethyl 4-iodobutyrate.

EXAMPLE 104 Preparation of 2-(3-carbethoxypropyl)cyclohexan-1-one

This compound is prepared from2-carbalkoxy(methyl/ethyl)-2-(3-carbethoxypropyl)cyclohexan-1-one(Example 13) by decarbalkoxylation according to the procedure describedin Example 11 followed by esterification by the procedure of Example 12.

EXAMPLE 105 Preparation of 2-(5-carbethoxypentyl)cyclohexan-1-one

This compound is prepared by alkylation of 2-cyclohexanone carboxylate(mixed methyl and ethyl esters) with ethyl-6-bromohexanoate according tothe procedure of Example 10, followed by decarbalkoxylation according tothe procedure of Example 11 and finally esterification by the procedureof Example 12.

EXAMPLE 106 Preparation of 2-(7-carbethoxyheptyl)cyclohexan-1-one

Alkylation of 2-cyclohexanone carboxylate (mixed methyl and ethylesters) with ethyl 8-bromoctanoate in accordance with the procedure ofExample 10, followed by decarbalkoxylation by the procedure of Example11 and then esterification by the procedure of Example 12 is productiveof the subject compound.

EXAMPLE 107 Preparation of ethyl7-(1-acetoxycyclohex-1-en-2-yl)heptanoate

A stirred solution of 28.0 g. of ethyl7-(cyclohexan-1-on-2-yl)heptanoate (Example 12), 170 mg. ofp-toluenesulfonic acid monohydrate, and 25.6 g. of acetic anhydride isheated for 5 hours while allowing 8.0 g. of distillate to distill. Thecooled solution is poured into a stirred, ice-cold mixture of 500 ml. ofsaturated sodium bicarbonate and 250 ml. of hexane. After one hour thehexane phase is separated, dried, and evaporated. The crude product isdistilled to give a liquid, IR 1760 cm⁻¹ (vinyl ester carbonyl) and 1740cm⁻¹ (ethyl ester carbonyl).

EXAMPLE 108 Preparation of1-acetoxy-2-(3-carbethoxypropyl)cyclohex-1-ene

Treatment of 2-(3-carbethoxypropyl)cyclohexan-1-one (Example 14) withacetic anhydride by the procedure of Example 24 is productive of thesubject compound.

EXAMPLE 109 Preparation of1-acetoxy-2-(5-carbethoxypentyl)cyclohex-1-ene

Treatment of 2-(5-carbethoxypentyl)cyclohexan-1-one (Example 15) withacetic anhydride by the procedure of Example 24 is productive of thesubject compound.

EXAMPLE 110 Preparation of1-acetoxy-2-(7-carbethoxyheptyl)cyclohex-1-ene

Treatment of 2-(7-carbethoxyheptyl)cyclohexan-1-one (Example 16) withacetic anhydride by the procedure of Example 24 is productive of thesubject compound.

EXAMPLE 111 Preparation of ethyl 7-(cyclohex-2-en-1-one-2-yl)heptanoate

To a stirred solution of ethyl 7-(1-acetoxycyclohex-1-en-2-yl)heptanoate(Example 24) in 750 ml. of acetic acid and 125 ml. of pyridine at 10° C.is added a solution of 13.8 g. of bromine in 200 ml. of acetic acid over20 minutes. The resulting solution is allowed to stand at ambienttemperature for 45 minutes and is then decolorized with sodium sulfite.The solution is poured into 800 ml. of half-saturated sodium chlorideand extracted with 1:1 hexane-ether. The extract is washed successivelywith water and saturated sodium chloride, dried over sodium carbonate,and evaporated to give 32 g. of the crude bromoketone. To a stirredsuspension of 14.2 g. of lithium bromide and 16.6 g. of lithiumcarbonate in 250 ml. of anhydrous dimethylformamide at 80° C. is addedthe above bromoketone. The stirred mixture is heated to boiling over 20minutes and refluxed for 15 minutes. The cooled mixture is poured into1000 ml. of water, acidified with dilute hydrochloric acid, andextracted with ether. The extract is washed successively with water andsaturated sodium chloride, dried, and evaporated. The product ispurified by distillation to give a liquid, IR 1740 cm⁻¹ (estercarbonyl), 1685 cm⁻¹ (ketone carbonyl), and 1650 cm⁻¹ (olefin); NMR(CCl₄) 6.63 (multiplet, vinyl proton).

EXAMPLE 112 Preparation of 2-(3-carbethoxypropyl)cyclohex-2-en-1-one

In accordance with the procedure of Example 40, bromination of1-acetoxy-2-(3-carbethoxypropyl)cyclohex-1-ene (Example 25) followed bytreatment with lithium bromide and lithium carbonate is productive ofthe subject compound.

EXAMPLE 113 Preparation of 2-(5-carbethoxypentyl)cyclohex-2-en-1-one

By the procedure of Example 40, bromination of1-acetoxy-2-(5-carbethoxypentyl)cyclohex-1-ene (Example 26) followed bytreatment with lithium bromide and lithium carbonate is productive ofthe subject compound.

EXAMPLE 114 Preparation of 2-(7-carbethoxyheptyl)cyclohex-1-en-2-one

By the procedure of Example 40, bromination of1-acetoxy-2-(7-carbethoxyheptyl)cyclohex-1-ene (Example 27) followed bytreatment with lithium bromide and lithium carbonate is productive ofthe subject compound.

EXAMPLE 115 Preparation of2-(4-p-toluenesulfonyloxybutyl)-1-methoximino-2-cyclopentene

In the manner described in Example 34, treatment of2-(4-hydroxybutyl)-1-methoximino-2-cyclopentene with p-toluene sulfonylchloride in pyridine gives the subject product as a light yellow oil; IR(film): 1600, 1190, 1050, 885 cm⁻¹.

EXAMPLE 116 Preparation of2-(6-carbethoxy-5-thiahexyl)-1-methoximino-2-cyclopentene

To a stirred mixture of 1.465 g. (0.0348 mole) of sodium hydride (57.2%in mineral oil) in 50 ml. of dimethoxyethane, under nitrogen, is addedslowly 4.8 g. (0.0347 mole) of ethyl-2-mercaptoacetate. The reactionmixture is stirred at room temperature for one hour and then a solutionof 7.8 g. (0.0231 mole) of2-(4-p-toluenesulfonyloxybutyl)-1-methoximino-2-cyclopentene in 30 ml.of dimethoxyethane is added dropwise and stirred at room temperature for18 hours. The solution is heated at reflux for one hour, cooled andpoured into cold dilute hydrochloric acid and then extracted with ether.The combined ether extracts are washed with saline, dried over magnesiumsulfate and evaporated to give 7.6 g. of subject product as a yellowoil.

EXAMPLE 117 Preparation of 2-(6-carboxy-5-thiahexyl)-2-cyclopentenone

In the manner described in Example 38, treatment of2-(6-carbethoxy-5-thiahexyl)-1-methoximino-2-cyclopentene with acetoneand 2 N hydrochloric acid at reflux gives the subject product as ayellow oil.

EXAMPLE 118 Preparation of 2-(6-carbethoxy-5-thiahexyl)-2-cyclopentenone

In the manner described in Example 39, treatment of2-(6-carboxy-5-thiahexyl)-2-cyclopentenone with p-toluenesulfonic acidin ethanol gives the subject ester as a yellow oil.

EXAMPLE 119 Preparation of 3-triphenylmethoxy-1-octyne

A mixture of 1.26 g. (10.0 mmoles) of 1-octyn-3-ol, 4.85 g. (15.0mmoles) of triphenylmethyl bromide, and 50 ml. of dry pyridine is heatedat 95° C. for 60 minutes with occasional swirling. The solution iscooled, treated with water, and extracted with ether. The extract iswashed successively with water and saturated sodium chloride solution,dried over magnesium sulfate, and concentrated. The crude product ispurified by chromatography on Florisil and recrystallization frompetroleum ether to give white crystals, m.p. 65°-66.5°, νmax. (KBr) 3280(acetylenic hydrogen), 1605, 1030, and 702 cm⁻¹ (triphenylmethoxygroup).

EXAMPLE 120 Preparation of ethyl9-oxo-15-triphenylmethoxy-13-trans-8ξ-prostenoate

A stirred solution of 7.37 g. (20.0 mmoles) of3-triphenylmethoxy-1-octyne (Example 119) in 10 ml. of benzene istreated with 16.7 mg. of 1.2 M diisobutylaluminum hydride in hexane, andthe resulting solution is heated at 50° C. for 2 hours. The solution iscooled to 0° C. and treated with 10.5 ml. of 1.7 M methyl lithium inether. After stirring for a 20 minute period at ambient temperature, thealanate solution is cooled to 0° C. and treated with a solution of 3.98g. (16.7 mmoles) of 2-(6-carbethoxyhexyl)cyclopent-2-en-1-one (Example13) in 5 ml. of ether. The resulting solution is stirred at ambienttemperature for 22.5 hours, diluted with ether, and poured into astirred mixture 2 N acetic acid and ice. After stirring until methaneevolution ceases, the organic phase is separated and washed successivelywith water and saturated sodium chloride solution. The extract is driedover magnesium sulfate and concentrated. The crude product in theresidue is purified by chromatography on silica gel to give an oil,νmax. 1735 (carbonyl groups), 967 (trans vinyl group), and 705 cm⁻¹(triphenylmethoxy group).

EXAMPLE 121 Preparation of ethyl 15-hydroxy-9-oxo-13-trans-prostenoate

A 0.05 M solution of ethyl9-oxo-15-triphenylmethoxy-13-trans-8ξprostenoate (Example 120) inglacial acetic acid-tetrahydrofuran-water (4:2:1) is heated at 45° C.for 3.5 hours. The solvents are evaporated at reduced pressure, and theresidue is dissolved in ether. The solution is washed successively withwater, 0.5 N sodium bicarbonate solution, and saturated sodium chloridesolution; dried over magnesium sulfate; and concentrated. Columnchromatography of the crude product on silica gel gives two epimericsubstances which are purified separately by thin layer chromatography togive oils differing only in chromatographic behavior, νmax. 3470(hydroxyl group), 1735 (carbonyl groups), and 967 cm⁻¹ (trans vinylgroup).

EXAMPLE 122 Preparation of 15-hydroxy-9-oxo-13-trans-prostenoic acid

A solution of 2 g. of ethyl 15-hydroxy-9-oxo-13,14-trans-prostenoate(Example 121) (mixture of racemates) in 32 ml. of methanol-water (1:1),containing 850 mg. of potassium hydroxide is stirred at ambienttemperature for 18 hours. After acidification with 10% hydrochloricacid, the solution is extracted with ether several times. The combinedether extracts are washed with saturated sodium chloride solution, driedwith anhydrous magnesium sulfate and taken to dryness to give 1.69 g.(92%) of an oil which partially crystallizes. Recrystallized fromether-hexane gives white crystals, m.p. 79°-81° C.; nmrδ6.36 (s,hydroxyl and carboxyl groups), 5.61 (t, olefinic protons), 4.12 (s, C₁₃--H) and 0.90 (s, terminal methyl).

EXAMPLE 123 Preparation of tetrahydropyran-2-yl9-oxo-11-tetrahydropyranyloxy-15-triphenylmethoxy-13-trans-8ξ-prostenoate

In the manner described in Example 120, 13.6 g. (37 mmoles) of3-triphenylmethoxy-1-octyne (Example 119) contained in 18.5 ml. ofbenzene is converted to an alanate reagent by treatment with 31 ml. of1-2 M diisobutylaluminum hydride in hexane and 21 ml. of 1.7 M methyllithium in ether. To the stirred, ice-cold reagent is added a solutionof 10.97 g. (24.6 mmoles) of2-(6-tetrahydropyranylcarboxyhexyl)-4-tetrahydropyranyloxycyclopent-2-en-1-one(Example 95) in 10 ml. of ether during 10 minutes. The resultingsolution is stirred at ambient temperature for 20 hours, diluted withether, and poured into a stirred mixture of 2 N hydrochloric acid andice. The organic phase is separated and washed successively with waterand saturated sodium chloride solution. The extract is dried overmagnesium sulfate, and the solvents are evaporated at reduced pressureto give the crude product as an oil, νmax. 1735 (carbonyl groups), 1030(tetrahydropyranyloxy groups), 970 (trans vinyl group), and 705 cm⁻¹(triphenylmethoxy group).

EXAMPLE 124 Preparation of 11,15-dihydroxy-9-oxo-13-trans-prostenoicacids

A 0.05 M solution of crude tetrahydropyran-2-yl9-oxo-11-tetrahydropyranyloxy-15-triphenylmethoxy-13-trans-prostenoate(Example 123) in glacial acetic acid-tetrahydrofuran-water (4:2:1) isheated at 45° C. for 3.5 hours. The solution is diluted with water andextracted with ether. The extract is washed successively with water andsaturated sodium chloride solution and dried over magnesium sulfate. Thesolvents are removed at reduced pressure. Column chromatography of theresidue on acid-washed silica gel gives the title compounds as a pair ofepimeric substances which are purified separately by partitionchromatography.

The fast-running epimer (15-epi-d,1-prostaglandin E.) is obtained as anoil, νmax, 1735 (ketone carbonyl group), 1710 (acid carbonyl group), and967 cm⁻¹ (trans vinyl group); NMR (acetone-d₆) 5.68 (multiplet, vinylhydrogens) and 4.11 δ(multiplet, carbinolic hydrogens).

The slow-running epimer (d,1-prostaglandin E₁) is recrystallized fromethyl acetate-petroleum ether to give white crystals, m.p. 100°-105° C.,νmax. (KBr) 1725 (ketone carbonyl group), 1700 (acid carbonyl group),and 970 cm⁻¹ (trans vinyl group); NMR (acetone-d₆) 5.67 (multiplet,vinyl hydrogens) and 4.12 (multiplet, carbinolic hydrogens).

EXAMPLES 125 TO 139

In accordance with the method described in Example 119, the various3-hydroxy-1-alkynes listed in the table below are converted to thecorresponding 3-triphenylmethoxy-1-alkynes by treatment withtriphenylmethyl bromide.

                  TABLE                                                           ______________________________________                                        125  1-heptyn-3-ol    3-triphenylmethoxyheptyno-1                             126  1-hexyn-3-ol     3-triphenylmethoxy-hexyne-1                             127  1-pentyn-3-ol    3-triphenylmethoxy-pentyne-1                            128  1-nonyne-3-ol.sup.a                                                                            3-triphenylmethoxy-nonyne-1                             129  1-decyno-3-ol.sup.b                                                                            3-triphenylmethoxy-decyne-1                             130  4-ethyl-1-octyne-3-ol                                                                          3-triphenylmethoxy-4-ethyl-                                                   octyne-1                                                131  4-ethyl-1-hexyne-3-ol                                                                          3-triphenylmethoxy-4-ethyl-                                                   hexyne-1                                                132  4-methyl-1-heptyne-3-ol                                                                        3-triphenylmethoxy-4-methyl-                                                  eptyne-1                                                133  4-methyl-1-pentyne-3-ol                                                                        3-triphenylmethoxy-4-methyl-                                                  pentyne-1                                               134  7-methyl-6-en-1-octyne-                                                                        3-triphenylmethoxy-7-methyl-                                 3-ol.sup.c       6-en-octyne-1                                           135  6,7-demethyl-6-en-1-                                                                           3-triphenylmethoxy-6,7-                                      octyne-3-ol.sup.c                                                                              dimethyl-6-en-octyne-1                                  136  7-isobutyl-6-en-1-                                                                             3-triphenylmethoxy-7-isobutyl-                               octyne-3-ol.sup.c                                                                              6-en-octyne-1                                           137  5-en-1-hexyne-3-ol.sup.d                                                                       3-triphenylmethoxy-5-en-                                                      hexyne-1                                                138  5,9-dimethyl-9-en-1-                                                                           3-triphenylmethoxy-5,9-                                      decyne-3-ol.sup.e                                                                              dimethyl-9-en-decyne-1                                  139  cis-5-en-1-octyne-3-                                                                           3-triphenylmethoxy-cis-5-en-                                 ol.sup.f         octyne-1                                                ______________________________________                                         References:-                                                                  .sup.a M. Bertrand, Bull. Soc. Chim. France, 461 (1956).                      .sup.b F. Bohlmann and D. Ratz, Chem. Ber., 90, 2265 (1957).                  .sup.c U.S. Pat. No. 3,458,105 (June 24, 1969); Chem. As., 71, 60678          (1969).                                                                       .sup.d A. Viola and J.H. MacMillan, Jour. Amer. Chem. Soc., 92,2404           (1970).                                                                       .sup.e Sequin, Bull. Soc. Chim. France, 12, 948 (1945).                       .sup.f J. Fried et al., Jour. Amer. Chem. Soc., 94, 4342 (1972).         

EXAMPLES 140-256

Treatment of the cycloalkenone designated in the table below with thealanate [lithiumdiisobutyl-methyl-(3-triphenylmethoxy-1-trans-alkenyl)-alanate] preparedby treatment of the listed 3-triphenylmethoxy-1-alkyne with diisobutylaluminum hydride followed with methyl lithium, all by the proceduredescribed in Example 120, is productive9-oxo-15-triphenylmethoxy-13-trans-8-ξ-prostenoates of the table.

                                      TABLE 3                                     __________________________________________________________________________                     Starting 3-triphenyl-                                                                   Product                                                 Starting Cycloalkenone                                                                    methoxy-1-alkyne of                                                                     Alkyl 9-oxo-15-triphenylmethoxy-13-trans-          Example                                                                            of Example  Example                                                      8ξ-prostenoate                                                             __________________________________________________________________________    140  14          119       ethyl 9-oxo-15-triphenylmethoxy-5,6,7-tri-                                    nor-13-trans-8ξ-prostenoate                     141  23          119       ethyl 9-oxo-15-triphenylmethoxy-7a,7b-bis-                                    homo-13-trans-8ξ-prostenoate                    142  31          119       ethyl 9-oxo-15-triphenylmethoxy-2-ethyl-13-                                   trans-8ξ-prostenoate                            143  41          119       ethyl 9-oxo-15-triphenylmethoxy-3,3-dimethyl-                                 13-trans-8ξ-prostenoate                         144  46          119       ethyl 9-oxo-15-triphenylmethoxy-3-oxa-13-                                     trans-8ξ-prostenoate                            145  53          119       ethyl 9-oxo-15-triphenylmethoxy-7-nor-13-                                     trans-8ξ-prostenoate                            146  70          119       ethyl 9-oxo-15-triphenylmethoxy-2-fluoro-13-                                  trans-8ξ-prostenoate                            147  74          119       ethyl 9-oxo-15-triphenylmethoxy-7a-homo-13-                                   13-trans-8ξ-prostenoate                         148  79          119       ethyl 9-oxo-15-triphenylmethoxy-2-phenyl-13-                                  trans-8ξ-prostenoate                            149  99          119       ethyl 9-oxo-15-triphenylmethoxy-2-methyl-13-                                  trans-8ξ-prostenoate                            150  111         119       ethyl 9-oxo-15-triphenylmethoxy-10a-homo-13-                                  trans-8ξ-prostenoate                            151  112         119       ethyl 9-oxo-15-triphenylmethoxy-10a-homo-5,-                                  6,7-trinor-13-trans-8ξ-prostenoate              152  113         119       ethyl 9-oxo-15-triphenylmethoxy-10a-homo-7-                                   nor-13-trans-8ξ-prostenoate                     153  114         119       ethyl 9-oxo-15-triphenylmethoxy-7a,10a-bis-                                   homo-13-trans-8ξ-prostenoate                    154  118         119       ethyl 9-oxo-15-triphenylmethoxy-3-thia-13-                                    13-trans-8ε-prostenoate                    155  81          119       butyl 9-oxo-15-triphenylmethoxy-13-trans-8ξ-                               4                                                                             prostenoate                                        156  82          119       isopropyl 9-oxo-15-triphenylmethoxy-13-trans-                                 8ξ-prostenoate                                  157  83          119       methyl 9-oxo-15-triphenylmethoxy-13-trans-8ξ                               -                                                                             prostenoate                                        158  84          119       n-decyl 9-oxo-15-triphenylmethoxy-13-trans-                                   8ξ-prostenoate                                  159  900         119       methyl 9-oxo-15-triphenylmethoxy-5-cis,13-                                    trans-8ξ-prostadienoate                         160  13          125       ethyl 9-oxo-15-triphenylmethoxy-20-nor-13-                                    trans-8ξ-prostenoate                            161  13          128       ethyl 9-oxo-15-triphenylmethoxy-20-methyl-                                    13-trans-8ξ-prostenoate                         162  13          130       ethyl 9-oxo-15-triphenylmethoxy-16-ethyl-13-                                  trans-8ξ-prostenoate                            163  13          132       ethyl 9-oxo-15-triphenylmethoxy-16-methyl-20-                                 nor-13-trans-8ξ-prostenoate                     164  13          134       ethyl 9-oxo-15-triphenylmethoxy-19-methyl-13-                                 trans,18-8ξ-prostadienoate                      165  13          135       ethyl 9-oxo-15-triphenylmethoxy-18,19-di-                                     methyl-13-trans,18-8ξ-prostadienoate            166  13          139       ethyl 9-oxo-15-triphenylmethoxy-8ξ-13-trans,                               17-cis-prostadienoate                              167  14          139       ethyl 9-oxo-15-triphenylmethoxy-5,6,7-trinor-                                 8ξ-13-trans,17-cis-prostadienoate               168  15          139       ethyl 9-oxo-15-triphenylmethoxy-6,7-dinor-8ξ                               -                                                                             13-trans,17-cis-prostadienoate                     169  23          139       ethyl 9-oxo-15-triphenylmethoxy-7a,7b-bishomo-                                8ξ-13-trans,17-cis-prostadienoate               170  31          139       ethyl 9-oxo-15-triphenylmethoxy-2-ethyl-8ξ-1                               3-                                                                            trans,17-cis-prostadienoate                        171  41          139       ethyl 9-oxo-15-triphenylmethoxy-3,3-dimethyl-                                 8ξ-13-trans,17-cis-prostadienoate               172  46          139       ethyl 9-oxo-15-triphenylmethoxy-3-oxa-8ξ-13-                               trans,17-cis-prostadienoate                        173  53          139       ethyl 9-oxo-15-triphenylmethoxy-7-nor-8ξ-13-                               trans,17-cis-prostadienoate                        174  70          139       ethyl 9-oxo-15-triphenylmethoxy-2-fluoro-8ξ-                               13-                                                                           trans,17-cis-prostadienoate                        175  74          139       ethyl 9-oxo-15-triphenylmethoxy-7a-homo-8ξ-1                               3-                                                                            trans,17-cis-prostadienoate                        176  79          139       ethyl 9-oxo-15-triphenylmethoxy-2-phenyl-8ξ-                               13-                                                                           trans,17-cis-prostadienoate                        177  99          139       ethyl 9-oxo-15-triphenylmethoxy-2-methyl-8ξ-                               13-                                                                           trans,17-cis-prostadienoate                        178  111         139       ethyl 9-oxo-15-triphenylmethoxy-10a-homo-8ξ-                               13-                                                                           trans,17-cis-prostadienoate                        179  112         139       ethyl 9-oxo-15-triphenylmethoxy-10a-homo-5,6,7-                               trinor-13-trans,17-cis-prostadienoate              180  113         139       ethyl 9-oxo-15-triphenylmethoxy-10a-homo-7-nor-                               8ξ-13-trans,17-cis-prostadienoate               181  114         139       ethyl 9-oxo-15-triphenylmethoxy-7a,10a-bishomo-                               8ξ-13-trans,17-cis-prostadienoate               182  118         139       ethyl 9-oxo-15-triphenylmethoxy-3-thia-8ξ-13                               -                                                                             trans,17-cis-prostadienoate                        183  81          139       butyl 9-oxo-15-triphenylmethoxy-8ξ-13-trans,                               17-                                                                           cis-prostadienoate                                 184  82          139       isopropyl 9-oxo-15-triphenylmethoxy-8ξ-13-tr                               ans,                                                                          cis-prostadienoate                                 185  83          139       methyl 9-oxo-15-triphenylmethoxy-8ξ-13-trans                               ,                                                                             17-cis-prostadienoate                              186  84          139       n-decyl 9-oxo-15-triphenylmethoxy-8ξ-13-tran                               s,17-                                                                         cis-prostadienoate                                 187  14          136       ethyl 9-oxo-15-triphenylmethoxy-5,6,7-trinor-19                               -                                                                             isobutyl-8ξ-13-trans,18-prostadienoate          188  14          137       ethyl 9-oxo-15-triphenylmethoxy-5,6,7,19,20-pen                               ta-                                                                           nor-8ξ-13-trans-17,prostadienoate               189  13          137       ethyl 9-oxo-15-triphenylmethoxy-19,20-dinor-8.x                               i.-13-                                                                        trans,18-prostadienoate                            190  13          138       ethyl 9-oxo-15-triphenylmethoxy-17-methyl-20-is                               o-                                                                            propenyl-8ξ-trans-prostenoate                   191  15          131       ethyl 9-oxo-15-triphenylmethoxy-16-ethyl-6,7,19                               ,                                                                             20-tetranor-8ξ-13-trans-prostenoate             192  15          135       ethyl 9-oxo-15-triphenylmethoxy-18,19-dimethyl-                               6,                                                                            7-dinor-8ξ-13-trans,18-prostadienate            193  23          130       ethyl 9-oxo-15-triphenylmethoxy-16-ethyl-7a,7b-                               bishomo-8ξ-13-trans-prostenoate                 194  23          134       ethyl 9-oxo-15-triphenylmethoxy-19-methyl-7a,7b                               -                                                                             bishomo-8ξ-13-trans,18-prostadienoate           195  31          126       ethyl 9-oxo-15-triphenylmethoxy-2-ethyl-19,20-                                dinor-8ξ-13-trans-prostenoate                   196  31          129       ethyl 9-oxo-15-triphenylmethoxy-2,20-diethyl-                                 8ξ-13-trans-prostenoate                         197  31          132       ethyl 9-oxo-15-triphenylmethoxy-2-ethyl-16-                                   methyl-8ξ-20-nor-13-trans-prostenoate           198  31          135       ethyl 9-oxo-15-triphenylmethoxy-2-ethyl-18,                                   19-dimethyl-8ξ-13-trans,18-prostadienoate       199  41          127       ethyl 9-oxo-15-triphenylmethoxy-3,3-dimethyl-                                 18,19,20-trinor-8ξ-13-trans-prostenoate         200  41          128       ethyl 9-oxo-15-triphenylmethoxy-3,3,20-tri-                                   methyl-8ξ-13-trans-prostenoate                  201  41          132       ethyl 9-oxo-15-triphenylmethoxy-3,3,16-tri-                                   methyl-20-nor-8ξ-13-trans-prostenoate           202  41          136       ethyl 9-oxo-15-triphenylmethoxy-3,3-dimethyl-                                 19-isobutyl-8ξ-13-trans,18-prostadienoate       203  41          137       ethyl 9-oxo-15-triphenylmethoxy-3,3-dimethyl-                                 19,20-dinor-8ξ-13-trans,17-prostadienoate       204  46          125       ethyl 9-oxo-15-triphenylmethoxy-3-oxa-20-nor-                                 8ξ-13-trans-prostenoate                         205  46          128       ethyl 9-oxo-15-triphenylmethoxy-3-oxa-20-                                     methyl-8ξ-13-trans-prostenoate                  206  46          130       ethyl 9-oxo-15-triphenylmethoxy-3-oxa-16-                                     ethyl-8ξ-13-trans-prostenoate                   207  46          132       ethyl 9-oxo-15-triphenylmethoxy-3-oxa-16-                                     methyl-20-nor-8ξ-13-trans-prostenoate           208  46          137       ethyl 9-oxo-15-triphenylmethoxy-3-oxa-19,20-                                  dinor-8ξ-13-trans,17-prostadienoate             209  53          137       ethyl 9-oxo-15-triphenylmethoxy-7,19,20-tri-                                  nor-8ξ-13-trans,17-prostadienoate               210  53          135       ethyl 9-oxo-15-triphenylmethoxy-7-nor-18,19-                                  dimethyl-8ξ-13-trans,18-prostadienoate          211  53          133       ethyl 9-oxo-15-triphenylmethoxy-7,18,19,20-                                   tetranor-16-methyl-8ξ-13-trans-prostenoate      212  70          125       ethyl 9-oxo-15-triphenylmethoxy-2-fluoro-20-                                  nor-8ξ-13-trans-prostenoate                     213  70          129       ethyl 9-oxo-15-triphenylmethoxy-2-fluoro-20-                                  ethyl-8ξ-13-trans-prostenoate                   214  70          131       ethyl 9-oxo-15-triphenylmethoxy-2-fluoro-16-                                  ethyl-19,20-dinor-8ξ  -13-trans-prostenoate     215  70          132       ethyl 9-oxo-15-triphenylmethoxy-2-fluoro-16-                                  methyl-20-nor-8ξ-13-trans-prostenoate           216  70          134       ethyl 9-oxo-15-triphenylmethoxy-2-fluoro-19-                                  methyl-8ξ-13-trans,18-prostadienoate            217  74          135       ethyl 9-oxo-15-triphenylmethoxy-7a-homo-18,19-                                dimethyl-8ξ-13-trans,18-prostadienoate          218  74          137       ethyl 9-oxo-15-triphenylmethoxy-7a-homo-19,20-                                dinor-8ξ-13-trans,17-prostadienoate             219  79          125       ethyl 9-oxo-15-triphenylmethoxy-2-phenyl-20-                                  nor-8ξ-13-trans-prostenoate                     220  79          129       ethyl 9-oxo-15-triphenylmethoxy-2-phenyl-20-                                  ethyl-8ξ-13-trans-prostenoate                   221  79          130       ethyl 9-oxo-15-triphenylmethoxy-2-phenyl-16-                                  ethyl-8ξ-13-trans-prostenoate                   222  79          133       ethyl 9-oxo-15-triphenylmethoxy-2-phenyl-16-                                  methyl-18,19,20-trinor-8ξ-trans-prostenoate     223  79          135       ethyl 9-oxo-15-triphenylmethoxy-2-phenyl-18,                                  19,-dimethyl-8ξ-13-trans,18-prostadienoate      224  99          125       ethyl 9-oxo-15-triphenylmethoxy-2-methyl-20-                                  nor-8ξ-13-trans-prostenoate                     225  99          126       ethyl 9-oxo-15-triphenylmethoxy-2,20-dimethyl-                                8ξ-13-trans-prostenoate                         226  99          131       ethyl 9-oxo-15-triphenylmethoxy-2-methyl-16-                                  ethyl-19,20-dinor-8ξ-13-trans-prostenoate       227  99          134       ethyl 9-oxo-15-triphenylmethoxy-2,19-dimethyl-                                8ξ-13-trans,18-prostadienoate                   228  99          137       ethyl 9-oxo-15-triphenylmethoxy-2-methyl-19,                                  20-dinor-8ξ-13-trans,17-prostadienoate          229  111         125       ethyl 9-oxo-15-triphenylmethoxy-10a-homo-20-                                  nor-8ξ-13-trans-prostenoate                     230  111         128       ethyl 9-oxo-15-triphenylmethoxy-10a-homo-20-                                  methyl-8ξ-13-trans-prostenoate                  231  111         130       ethyl 9-oxo-15-triphenylmethoxy-10a-homo-16-                                  ethyl-8ξ-13-trans-prostenoate                   232  111         135       ethyl 9-oxo-15-triphenylmethoxy-10a-homo-18,                                  19-dimethyl-8ξ-13-trans,18-prostadienoate       233  111         137       ethyl 9-oxo-15-triphenylmethoxy-10a-homo-19,                                  20-dinor-8ξ-13-trans,17-prostadienoate          234  112         129       ethyl 9-oxo-15-triphenylmethoxy-10a-homo-5,6,                                 7-trinor-20-ethyl-8ξ-13-trans-prostenoate       235  112         132       ethyl 9-oxo-15-triphenylmethoxy-10a-homo-5,6,                                 7,20-tetranor-16-methyl-8ξ-13-trans-prost-                                 enoate                                             236  112         136       ethyl 9-oxo-15-triphenylmethoxy-10a-homo-5,6,7-                               trinor-19-isobutyl-8ξ-13-trans,18-prostadien                               oate                                               237  113         128       ethyl 9-oxo-15-triphenylmethoxy-10a-homo-20-                                  methyl-8ξ-13-trans-prostenoate                  238  113         134       ethyl 9-oxo-15-triphenylmethoxy-10a-homo-19-                                  methyl-8ξ-13-trans,18-prostadienoate            239  114         125       ethyl 9-oxo-15-triphenylmethoxy-7a,10a-bis-                                   homo-20-nor-8ξ-13-trans-prostenoate             240  114         129       ethyl 9-oxo-15-triphenylmethoxy-7a,10a-bis-                                   homo-20-ethyl-8ξ-13-trans-prostenoate           241  114         132       ethyl 9-oxo-15-triphenylmethoxy-7a,10a-bis-                                   homo-16-methyl-20-nor-8ξ-13-trans-prostenoat                               e                                                  242  114         134       ethyl 9-oxo-15-triphenylmethoxy-7a,10a-bis-                                   homo-19-methyl-8ξ-13-trans,18-prostadienoate    243  118         125       ethyl 9-oxo-15-triphenylmethoxy-3-thia-20-nor-                                8ξ-13-trans-prostenoate                         244  118         128       ethyl 9-oxo-15-triphenylmethoxy-3-thia-20-methy                               l-                                                                            8ξ-13-trans-prostenoate                         245  118         130       ethyl 9-oxo-15-triphenylmethoxy-3-thia-16-ethyl                               -                                                                             8ξ-13-trans-prostenoate                         246  118         133       ethyl 9-oxo-15-triphenylmethoxy-3-thia-16-                                    methyl-18,19,20-trinor-8ξ-13-trans-prostenoa                               te                                                 247  118         134       ethyl 9-oxo-15-triphenylmethoxy-3-thia-19-methy                               l-                                                                            8ξ-13-trans,18-prostadienoate                   248  118         137       ethyl 9-oxo-15-triphenylmethoxy-3-thia-19,20-                                 dinor-8ξ-13-trans,17-prostadienoate             249  900         125       methyl 9-oxo-15-triphenylmethoxy-20-nor-8ξ-5                               -                                                                             cis,13-trans-prostadienoate                        250  900         128       methyl 9-oxo-15-triphenylmethoxy-20-methyl-8.xi                               .-5-                                                                          cis,13-trans-prostadienoate                        251  900         130       methyl 9-oxo-15-triphenylmethoxy-16-ethyl-8ξ                               -5-                                                                           cis,13-trans-prostadienoate                        252  900         132       methyl 9-oxo-15-triphenylmethoxy-16-methyl-20-                                nor-8ξ-5-cis,13-trans-prostadienoate            253  900         134       methyl 9-oxo-15-triphenylmethoxy-19-methyl-8.xi                               .-5-                                                                          cis,13-trans,18-prostatrienoate                    254  900         135       methyl 9-oxo-15-triphenylmethoxy-18,19-dimethyl                               -                                                                             8ξ-5-cis,13-trans,18-prostatrienoate            255  900         137       methyl 9-oxo-15-triphenylmethoxy-19,20-dinor-8.                               xi.-                                                                          5-cis,13-trans,17-prostatrienoate                  256  900         139       methyl 9-oxo-15-triphenylmethoxy-8ξ-5-cis,13                               -                                                                             trans,17-cis-prostatrienoate                       __________________________________________________________________________

EXAMPLE 257 Preparation of ethyl 9α/β,15-dihydroxy-13-trans-prostenoate

A solution containing 3 g. of ethyl9-oxo-15-hydroxy-13-trans-prostenoate (Example 121) in 120 ml. ofabsolute alcohol containing 115 mg. of sodium borohydride is stirred atambient temperature for 18 hours. The solution is poured into 300 ml. ofsaturated sodium chloride solution and the oily precipitate is extractedwith ether. The ether is washed with saturated sodium chloride solution,dried with anhydrous magnesium sulfate and taken to dryness to givesubject product as an oil; λmax. 2195, 5178, 8.45μ; the product is amixture of 9α- and 9β-hydroxy derivatives.

EXAMPLE 258-374

Treatment of the designated 9-oxo-15-triphenylmethoxy derivatives listedin the table below, with glacial acetic acid-tetrahydropyran-water(4:2:1) in the manner described in Example 121 is productive of thecorresponding 15-hydroxy derivatives of the table. This acid treatmentalso ensures a trans-relationship between the two side-chains attachedto C₈ and C₁₂.

                  TABLE 4                                                         ______________________________________                                                Starting 15-tri-                                                              phenylmethoxy Product Alkyl 9-oxo-                                    Ex-     derivative of 15-hydroxy-13-trans-                                    ample   Example       prostenoates                                            ______________________________________                                        258     140           Ethyl 9-oxo-15-hydroxy-                                                       5,6,7-trinor-13-trans-                                                        prostenoate                                             259     141           Ethyl 9-oxo-15-hydroxy-                                                       7a,7b-bishomo-13-                                                             trans-prostenoate                                       260     142           Ethyl 9-oxo-15-hydroxy-                                                       2-ethyl-13-trans-                                                             prostenoate                                             261     143           Ethyl 9-oxo-15-hydroxy-                                                       3,3-dimethyl-13-trans-                                                        prostenoate                                             262     144           Ethyl 9-oxo-15-hydroxy-                                                       3-oxa-13-trans-                                                               prostenoate                                             263     145           Ethyl 9-oxo-15-hydroxy-                                                       7-nor-13-trans-                                                               prostenoate                                             264     146           Ethyl 9-oxo-15-hydroxy-                                                       2-fluoro-13-trans-                                                            prostenoate                                             265     147           Ethyl 9-oxo-15-hydroxy-                                                       7a-homo-13-trans-                                                             prostenoate                                             266     148           Ethyl 9-oxo-15-hydroxy-                                                       2-phenyl-13-trans-                                                            prostenoate                                             267     149           Ethyl 9-oxo-15-hydroxy-                                                       2-methyl-13-trans-                                                            prostenoate                                             268     150           Ethyl 9-oxo-15-hydroxy-                                                       10a-homo-13-trans-                                                            prostenoate                                             269     151           Ethyl 9-oxo-15-hydroxy-                                                       10a-homo-5,6,7-trinor-                                                        13-trans-prostenoate                                    270     152           Ethyl 9-oxo-15-hydroxy-                                                       10a-homo-7-nor-13-                                                            trans-prostenoate                                       271     153           Ethyl 9-oxo-15-hydroxy-                                                       7a,10a-bishomo-13-                                                            trans-prostenoate                                       272     154           Ethyl 9-oxo-15-hydroxy-                                                       3-thia-13-trans-                                                              prostenoate                                             273     155           Butyl 9-oxo-15-hydroxy-                                                       13-trans-prostenoate                                    274     156           Isopropyl 9-oxo-15-                                                           hydroxy-13-trans-                                                             prostenoate                                             275     157           Methyl 9-oxo-15-hydroxy-                                                      13-trans-prostenoate                                    276     158           n-decyl 9-oxo-15-                                                             hydroxy-13-trans-                                                             prostenoate                                             277     159           Methyl 9-oxo-15-                                                              hydroxy-5-cis,-13-                                                            trans-prostadienoate                                    278     160           Ethyl 9-oxo-15-hydroxy-                                                       20-nor-13-trans-                                                              prostenoate                                             279     161           Ethyl 9-oxo-15-hydroxy-                                                       20-methyl-13-trans-                                                           prostenoate                                             280     162           Ethyl 9-oxo-15-hydroxy-                                                       16-ethyl-13-trans-                                                            prostenoate                                             281     163           Ethyl 9-oxo-15-hydroxy-                                                       16-methyl-20-nor-13-                                                          trans-prostenoate                                       282     164           Ethyl 9-oxo-15-hydroxy-                                                       19-methyl-13-trans,18-                                                        prostadienoate                                          283     165           Ethyl 9-oxo-15-hydroxy-                                                       18,19-dimethyl-13-                                                            trans,18-prostadienoate                                 284     166           Ethyl 9-oxo-15-hydroxy-                                                       13-trans,17-cis-                                                              prostadienoate                                          285     167           Ethyl 9-oxo-15-hydroxy-                                                       5,6,7-trinor-13-trans,                                                        17-cis-prostadienoate                                   286     168           Ethyl 9-oxo-15-hydroxy-                                                       6,7-dinor-13-trans-                                                           17-cis-prostadienoate                                   287     169           Ethyl 9-oxo-15-hydroxy-                                                       7a,7b-bishomo-13-                                                             trans,17-cis-prosta-                                                          dienoate                                                288     170           Ethyl 9-oxo-15-hydroxy-                                                       2-ethyl-13-trans,17-                                                          cis-prostadienoate                                      289     171           Ethyl 9-oxo-15-hydroxy-                                                       3,3-dimethyl-13-trans,                                                        17-cis-prostadienoate                                   290     172           Ethyl 9-oxo-15-hydroxy-                                                       3-oxa-13-trans,17-cis                                                         prostadienoate                                          291     173           Ethyl 9-oxo-15-hydroxy-                                                       7-nor-13-trans,17-cis-                                                        prostadienoate                                          292     174           Ethyl 9-oxo-15-hydroxy-                                                       2-fluoro-13-trans,17-                                                         cis-prostadienoate                                      293     175           Ethyl 9-oxo-15-hydroxy-                                                       7a-homo-13-trans,17-                                                          cis-prostadienoate                                      294     176           Ethyl 9-oxo-15-hydroxy-                                                       2-phenyl-13-trans,17-                                                         cis-prostadienoate                                      295     177           Ethyl 9-oxo-15-hydroxy-                                                       2-methyl-13-trans,17-                                                         cis-prostadienoate                                      296     178           Ethyl 9-oxo-15-hydroxy-                                                       10a-homo-13-trans,17-                                                         cis-prostadienoate                                      297     179           Ethyl 9-oxo-15-hydroxy-                                                       10a-homo-5,6,7-trinor-                                                        13-trans,17-cis-prosta-                                                       dienoate                                                298     180           Ethyl 9-oxo-15-hydroxy-                                                       10a-homo-7-nor-13-                                                            trans,17-cis-prosta-                                                          dienoate                                                299     181           Ethyl 9-oxo-15-hydroxy-                                                       7a,10a-bishomo-13-                                                            trans,17-cis-prosta-                                                          dienoate                                                300     182           Ethyl 9-oxo-15-hydroxy-                                                       3-thia-13-trans,17-                                                           cis-prostadienoate                                      301     183           Butyl 9-oxo-15-hydroxy-                                                       13-trans,17-cis-                                                              prostadienoate                                          302     184           Isopropyl 9-oxo-15-                                                           hydroxy-13-trans,17-                                                          cis-prostadienoate                                      303     185           Methyl 9-oxo-15-hydroxy-                                                      13-trans,17-cis-                                                              prostadienoate                                          304     186           n-decyl 9-oxo-15-                                                             hydroxy-13-trans,17-                                                          cis-prostadienoate                                      305     187           Ethyl 9-oxo-15-hydroxy-                                                       5,6,7-trinor-19-iso-                                                          butyl-13-trans,18-                                                            prostadienoate                                          306     188           Ethyl 9-oxo-15-hydroxy-                                                       5,6,7,19,20-pentanor-                                                         13-trans,17-prosta-                                                           dienoate                                                307     189           Ethyl 9-oxo-15-hydroxy-                                                       19,20-dinor-13-trans,                                                         18-prostadienoate                                       308     190           Ethyl 9-oxo-15-hydroxy-                                                       17-methyl-20-isopro-                                                          penyl-13-trans-prosta-                                                        dienoate                                                309     191           Ethyl 9-oxo-15-hydroxy-                                                       16-ethyl-6,7,19,20-                                                           tetranor-13-trans-                                                            prostenoate                                             310     192           Ethyl 9-oxo-15-hydroxy-                                                       18,19-dimethyl-6,7-                                                           dinor-13-trans,18-                                                            prostadienoate                                          311     193           Ethyl 9-oxo-15-hydroxy-                                                       16-ethyl-7a,7b-bishomo-                                                       13-trans-prostenoate                                    312     194           Ethyl 9-oxo-15-hydroxy-                                                       19-methyl-7a,7b-bis-                                                          homo-13-trans,18-                                                             prostadienoate                                          313     195           Ethyl 9-oxo-15-hydroxy-                                                       2-ethyl-19,20-dinor-                                                          13-trans-prostenoate                                    314     196           Ethyl 9-oxo-15-hydroxy-                                                       2,20-diethyl-13-trans-                                                        prostenoate                                             315     197           Ethyl 9-oxo-15-hydroxy-                                                       2-ethyl-16-methyl-20-                                                         nor-trans-prostenoate                                   316     198           Ethyl 9-oxo-15-hydroxy-                                                       2-ethyl-18,19-dimethyl-                                                       13-trans,18-prosta-                                                           dienoate                                                317     199           Ethyl 9-oxo-15-hydroxy-                                                       3,3-dimethyl-18,19,20-                                                        trinor-13-trans-                                                              prostenoate                                             318     200           Ethyl 9-oxo-15-hydroxy-                                                       3,3,20-trimethyl-13-                                                          trans-prostenoate                                       319     201           Ethyl 9-oxo-15-hydroxy-                                                       3,3,16-trimethyl-20-                                                          nor-13-trans-prosta-                                                          noate                                                   320     202           Ethyl 9-oxo-15-hydroxy-                                                       3,3-dimethyl-19-iso-                                                          butyl-13-trans,18-                                                            prostadienoate                                          321     203           Ethyl 9-oxo-15-hydroxy-                                                       3,3-dimethyl-19,20-                                                           dinor-13-trans,17-                                                            prostadienoate                                          322     204           Ethyl 9-oxo-15-hydroxy-                                                       3-oxa-20-nor-13-trans-                                                        prostenoate                                             323     205           Ethyl 9-oxo-15-hydroxy-                                                       3-oxa-20-methyl-13-                                                           trans-prostenoate                                       324     206           Ethyl 9-oxo-15-hydroxy-                                                       3-oxa-16-ethyl-13-                                                            trans-prostenoate                                       325     207           Ethyl 9-oxo-15-hydroxy-                                                       3-oxa-16-methyl-20-                                                           nor-13-trans-                                                                 prostenoate                                             326     208           Ethyl 9-oxo-15-hydroxy-                                                       3-oxa-19,20-dinor-13-                                                         trans,17-prostadienoate                                 327     209           Ethyl 9-oxo-15-hydroxy-                                                       7,19,20-trinor-13-                                                            trans,17-prostadienoate                                 328     210           Ethyl 9-oxo-15-hydroxy-                                                       7-nor-18,19-dimethyl-                                                         13-trans,18-prosta-                                                           dienoate                                                329     211           Ethyl 9-oxo-15-hydroxy-                                                       7,18,19,20-tetranor-                                                          16-methyl-13-trans-                                                           prostenoate                                             330     212           Ethyl 9-oxo-15-hydroxy-                                                       2-fluoro-20-nor-13-                                                           trans-prostenoate                                       331     213           Ethyl 9-oxo-15-hydroxy-                                                       2-fluoro-20-ethyl-13-                                                         trans-prostenoate                                       332     214           Ethyl 9-oxo-15-hydroxy-                                                       2-fluoro-16-ethyl-19,                                                         20-dinor-13-trans-                                                            prostenoate                                             333     215           Ethyl 9-oxo-15-hydroxy-                                                       2-fluoro-16-methyl-20-                                                        nor-13-trans-prostenoate                                                      prostenoate                                             334     216           Ethyl 9-oxo-15-hydroxy-                                                       2-fluoro-19-methyl-13-                                                        trans,18-prostadienoate                                 335     217           Ethyl 9-oxo-15-hydroxy-                                                       7a-homo-18,19-dimethyl-                                                       13-trans,18-prosta-                                                           dienoate                                                336     218           Ethyl 9-oxo-15-hydroxy-                                                       7a-homo-19,20-dinor-                                                          13-trans,17-prosta-                                                           dienoate                                                337     219           Ethyl 9-oxo-15-hydroxy-                                                       2-phenyl-20-nor-13-                                                           trans-prostenoate                                       338     220           Ethyl 9-oxo-15-hydroxy-                                                       2-phenyl-20-ethyl-13-                                                         trans-prostenoate                                       339     221           Ethyl 9-oxo-15-hydroxy-                                                       2-phenyl-16-ethyl-13-                                                         trans-prostenoate                                       340     222           Ethyl 9-oxo-15-hydroxy-                                                       2-phenyl-16-methyl-18,                                                        19,20-trinor-13-trans-                                                        prostenoate                                             341     223           Ethyl 9-oxo-15-hydroxy-                                                       2-phenyl-18,19-di-                                                            methyl-13-trans,18-pro-                                                       stadienoate                                             342     224           Ethyl 9-oxo-15-hydroxy-                                                       2-methyl-20-nor-13-                                                           trans-prostenoate                                       343     225           Ethyl 9-oxo-15-hydroxy-                                                       2,20-dimethyl-13-trans-                                                       prostenoate                                             344     226           Ethyl 9-oxo-15-hydroxy-                                                       2-methyl-16-ethyl-19,                                                         20-dinor-13-trans-                                                            prostenoate                                             345     227           Ethyl 9-oxo-15-hydroxy-                                                       2,19-dimethyl-13-trans,                                                       18-prostadienoate                                       346     228           Ethyl 9-oxo-15-hydroxy-                                                       2-methyl-19,20-dinor-                                                         13-trans,17-prosta-                                                           dienoate                                                347     229           Ethyl 9-oxo-15-hydroxy-                                                       10a-homo-20-nor-13-                                                           trans-prostenoate                                       348     230           Ethyl 9-oxo-15-hydroxy-                                                       10a-homo-20-methyl-13-                                                        trans-prostenoate                                       349     231           Ethyl 9-oxo-15-hydroxy-                                                       10a-homo-16-ethyl-13-                                                         trans-prostenoate                                       350     232           Ethyl 9-oxo-15-hydroxy-                                                       10a-homo-18,19-dimethyl-                                                      13-trans,18-prosta-                                                           dienoate                                                351     233           Ethyl 9-oxo-15-hydroxy-                                                       10a-homo-19,20-dinor-                                                         13-trans,17-prosta-                                                           dienoate                                                352     234           Ethyl 9-oxo-15-hydroxy-                                                       10a-homo-5,6,7-trinor-                                                        20-ethyl-13-trans-                                                            prostenoate                                             353     235           Ethyl 9-oxo-15-hydroxy-                                                       10a-homo-5,6,7,20-                                                            tetranor-16-methyl-13-                                                        trans-prostenoate                                       354     236           Ethyl 9-oxo-15-hydroxy-                                                       10a-homo-5,6,7-trinor-                                                        19-isobutyl-13-trans,                                                         18-prostadienoate                                       355     237           Ethyl 9-oxo-15-hydroxy-                                                       10a-homo-20-methyl-13-                                                        trans-prostenoate                                       356     238           Ethyl 9-oxo-15-hydroxy-                                                       10a-homo-19-methyl-13-                                                        trans,18-prostadienoate                                 357     239           Ethyl 9-oxo-15-hydroxy-                                                       7a,10a-bishomo-20-nor-                                                        13-trans-prostenoate                                    358     240           Ethyl 9-oxo-15-hydroxy-                                                       7a,10a-bishomo-20-                                                            ethyl-13-trans-pro-                                                           stenoate                                                359     241           Ethyl 9-oxo-15-hydroxy-                                                       7a,10a-bishomo-16-                                                            methyl-20-nor-13-trans-                                                       prostenoate                                             360     242           Ethyl 9-oxo-15-hydroxy-                                                       7a,10a-bishomo-19-                                                            methyl-13-trans,18-                                                           prostadienoate                                          361     243           Ethyl 9-oxo-15-hydroxy-                                                       3-thia-20-nor-13-trans-                                                       prostenoate                                             362     244           Ethyl 9-oxo-15-hydroxy-                                                       3-thia-20-methyl-13-                                                          trans-prostenoate                                       363     245           Ethyl 9-oxo-15-hydroxy-                                                       3-thia-16-ethyl-13-                                                           trans-prostenoate                                       364     246           Ethyl 9-oxo-15-hydroxy-                                                       3-thia-16-methyl-18,19,                                                       20-trinor-13-trans-                                                           prostenoate                                             365     247           Ethyl 9-oxo-15-hydroxy-                                                       3-thia-19-methyl-13-                                                          trans,18-prostadienoate                                 366     248           Ethyl 9-oxo-15-hydroxy-                                                       3-thia-19,20-dinor-13-                                                        trans,17-prostadienoate                                 367     249           Methyl 9-oxo-15-hydroxy-                                                      20-nor-5-cis,13-trans-                                                        prostadienoate                                          368     250           Methyl 9-oxo-15-hydroxy-                                                      20-methyl-5-cis,13-                                                           trans-prostadienoate                                    369     251           Methyl 9-oxo-15-hydroxy-                                                      16-ethyl-5-cis,13-                                                            trans-prostadienoate                                    370     252           Methyl 9-oxo-15-hydroxy-                                                      16-methyl-20-nor-5-cis,                                                       13-trans-prostadienoate                                 371     253           Methyl 9-oxo-15-hydroxy-                                                      19-methyl-5-cis,13-                                                           trans,18-prosta-                                                              trienoate                                               372     254           Methyl 9-oxo-15-hydroxy-                                                      18,19-dimethyl-5-cis,                                                         13-trans,18-prosta-                                                           trienoate                                               373     255           Methyl 9-oxo-15-hydroxy-                                                      19,20-dinor-5-cis,13-                                                         trans,17-prosta-                                                              trienoate                                               374     256           Methyl 9-oxo-15-hydroxy-                                                      5-cis,13-trans,17-cis-                                                        prostatrienoate                                         ______________________________________                                    

EXAMPLES 375-491

Saponification of the alkyl esters designated in the following table bythe method described in Example 122 is productive of the prostenoicacids of the table.

                  TABLE 5                                                         ______________________________________                                                Starting alkyl 9-                                                                           Product                                                 Ex-     oxo-prostenoate                                                                             9-Oxo-15-hydroxy-13-                                    ample   of example    trans-prostenoic acid                                   ______________________________________                                        375     258           9-oxo-15-hydroxy-5,6,7-                                                       trinor-13-trans-pros-                                                         tenoic acid                                             376     259           9-oxo-15-hydroxy-7a,7b-                                                       bishomo-13-trans-pros-                                                        tenoic acid                                             377     260           9-oxo-15-hydroxy-2-                                                           ethyl-13-trans-pros-                                                          tenoic acid                                             378     261           9-oxo-15-hydroxy-3,3-                                                         dimethyl-13-trans-                                                            prostenoic acid                                         379     262           9-oxo-15-hydroxy-3-oxa-                                                       13-trans-prostenoic                                                           acid                                                    380     263           9-oxo-15-hydroxy-7-nor-                                                       13-trans-prostenoic                                                           acid                                                    381     264           9-oxo-15-hydroxy-2-                                                           fluoro-13-trans-pros-                                                         tenoic acid                                             382     265           9-oxo-15-hydroxy-7a-                                                          homo-13-trans-pros-                                                           tenoic acid                                             383     266           9-oxo-15-hydroxy-2-                                                           phenyl-13-trans-pros-                                                         tenoic acid                                             384     267           9-oxo-15-hydroxy-2-                                                           methyl-13-trans-pros-                                                         tenoic acid                                             385     268           9-oxo-15-hydroxy-10a-                                                         homo-13-trans-pros-                                                           tenoic acid                                             386     269           9-oxo-15-hydroxy-10a-                                                         homo-5,6,7-trinor-13-                                                         trans-prostenoic acid                                   387     270           9-oxo-15-hydroxy-10a-                                                         homo-7-nor-13-trans-                                                          prostenoic acid                                         388     271           9-oxo-15-hydroxy-7a,-                                                         10a-bishomo-13-trans-                                                         prostenoic acid                                         389     272           9-oxo-15-hydroxy-3-                                                           thia-13-trans-pros-                                                           tenoic acid                                             390     273           9-oxo-15-hydroxy-13-                                                          trans-prostenoic acid                                   391     274           9-oxo-15-hydroxy-13-                                                          trans-prostenoic acid                                   392     275           9-oxo-15-hydroxy-13-                                                          trans-prostenoic acid                                   393     276           9-oxo-15-hydroxy-13-                                                          trans-prostenoic acid                                   394     277           9-oxo-15-hydroxy-5-cis,                                                       13-trans-prostadienoic                                                        acid                                                    395     278           9-oxo-15-hydroxy-20-nor-                                                      13-trans-prostenoic                                                           acid                                                    396     279           9-oxo-15-hydroxy-20-                                                          methyl-13-trans-pros-                                                         tenoic acid                                             397     280           9-oxo-15-hydroxy-16-                                                          ethyl-13-trans-pros-                                                          tenoic acid                                             398     281           9-oxo-15-hydroxy-16-                                                          methyl-20-nor-13-trans-                                                       prostenoic acid                                         399     282           9-oxo-15-hydroxy-19-                                                          methyl-13-trans,18-                                                           prostadienoic acid                                      400     283           9-oxo-15-hydroxy-18,19-                                                       dimethyl-13-trans,18-                                                         prostadienoic acid                                      401     284           9-oxo-15-hydroxy-13-                                                          trans,17-cis-prosta-                                                          dienoic acid                                            402     285           9-oxo-15-hydroxy-5,6,7-                                                       trinor-13-trans,17-cis-                                                       prostadienoic acid                                      403     286           9-oxo-15-hydroxy-6,7-di-                                                      nor-13-trans,17-cis-                                                          prostadienoic acid                                      404     287           9-oxo-15-hydroxy-7a,7b-                                                       bishomo-13-trans,17-                                                          cis-prostadienoic acid                                  405     288           9-oxo-15-hydroxy-2-                                                           ethyl-13-trans,17-cis-                                                        prostadienoic acid                                      406     289           9-oxo-15-hydroxy-3,3-                                                         dimethyl-13-trans,17-                                                         cis-prostadienoic acid                                  407     290           9-oxo-15-hydroxy-3-oxa-                                                       13-trans,17-cis-pros-                                                         tadienoic acid                                          408     291           9-oxo-15-hydroxy-7-nor-                                                       13-trans,17-cis-pros-                                                         tadienoic acid                                          409     292           9-oxo-15-hydroxy-2-                                                           fluoro-13-trans,17-cis-                                                       prostadienoic acid                                      410     293           9-oxo-15-hydroxy-7a-                                                          homo-13-trans,17-cis-                                                         prostadienoic acid                                      411     294           9-oxo-15-hydroxy-2-                                                           phenyl-13-trans,17-cis-                                                       prostadienoic acid                                      412     295           9-oxo-15-hydroxy-2-                                                           methyl-13-trans,17-                                                           cis-prostadienoic acid                                  413     296           9-oxo-15-hydroxy-10a-                                                         homo-13-trans,17-cis-                                                         prostadienoic acid                                      414     297           9-oxo-15-hydroxy-10a-                                                         homo-5,6,7-trinor-13-                                                         trans,17-cis-prosta-                                                          dienoic acid                                            415     298           9-oxo-15-hydroxy-10a-                                                         homo-7-nor-13-trans,-                                                         17-cis-prostadienoic                                                          acid                                                    416     299           9-oxo-15-hydroxy-7a,-                                                         10a-bishomo-13-trans,-                                                        17-cis-prostadienoic                                                          acid                                                    417     300           9-oxo-15-hydroxy-3-thia-                                                      13-trans,17-cis-prosta-                                                       dienoic acid                                            418     301           9-oxo-15-hydroxy-13-                                                          trans,17-cis-prosta-                                                          dienoic acid                                            419     302           9-oxo-15-hydroxy-13-                                                          trans,17-cis-prosta-                                                          dienoic acid                                            420     303           9-oxo-15-hydroxy-13-                                                          trans,17-cis-prosta-                                                          dienoic acid                                            421     304           9-oxo-15-hydroxy-13-                                                          trans,17-cis-prosta-                                                          dienoic acid                                            422     305           9-oxo-15-hydroxy-5,6,7-                                                       trinor-19-isobutyl-13-                                                        trans,18-prostadienoic                                                        acid                                                    423     306           9-oxo-15-hydroxy-5,6,7-                                                       19,20-pentanor-13-trans,                                                      17-prostadienoic acid                                   424     307           9-oxo-15-hydroxy-19,20-                                                       dinor-13-trans,18-                                                            prostadienoic acid                                      425     308           9-oxo-15-hydroxy-17,-                                                         methyl-20-isopropenyl-                                                        13-trans-prostenoic                                                           acid                                                    426     309           9-oxo-15-hydroxy-16-                                                          ethyl-6,7,19,20-tetra-                                                        nor-13-trans-prostenoic                                                       acid                                                    427     310           9-oxo-15-hydroxy-18,19-                                                       dimethyl-6,7-dinor-13-                                                        trans,18-prostadienoic                                                        acid                                                    428     311           9-oxo-15-hydroxy-16-                                                          ethyl-7a,7b-bishomo-                                                          13-trans-prostenoic                                                           acid                                                    429     312           9-oxo-15-hydroxy-19-                                                          methyl-7a,7b-bishomo-                                                         13-trans,18-prosta-                                                           dienoic acid                                            430     313           9-oxo-15-hydroxy-2-                                                           ethyl-19,20-dinor-13-                                                         trans-prostenoic acid                                   431     314           9-oxo-15-hydroxy-2,20-                                                        diethyl-13-trans-pros-                                                        enoic acid                                              432     315           9-oxo-15-hydroxy-2-                                                           ethyl-16-methyl-20-nor-                                                       13-trans-prostenoic                                                           acid                                                    433     316           9-oxo-15-hydroxy-2-                                                           ethyl-18,19-dimethyl-                                                         13-trans,18-prosta-                                                           dienoic acid                                            434     317           9-oxo-15-hydroxy-3,3-                                                         dimethyl-18,19,20-tri-                                                        nor-13-trans-prostenoic                                                       acid                                                    435     318           9-oxo-15-hydroxy-3,3,-                                                        20-trimethyl-13-trans-                                                        prostenoic acid                                         436     319           9-oxo-15-hydroxy-3,3,-                                                        16-trimethyl-20-nor-13-                                                       trans-prostenoic acid                                   437     320           9-oxo-15-hydroxy-3,3-                                                         dimethyl-19-isobutyl-                                                         13-trans,18-prosta-                                                           dienoic acid                                            438     321           9-oxo-15-hydroxy-3,3-                                                         dimethyl-19,20-dinor-                                                         13-trans,17-prosta-                                                           dienoic acid                                            439     322           9-oxo-15-hydroxy-3-oxa-                                                       20-nor-13-trans-prost-                                                        enoic acid                                              440     323           9-oxo-15-hydroxy-3-oxa-                                                       20-methyl-13-trans-                                                           prostenoic acid                                         441     324           9-oxo-15-hydroxy-3-oxa-                                                       16-ethyl-13-trans-                                                            prostenoic acid                                         442     325           9-oxo-15-hydroxy-3-oxa-                                                       16-methyl-20-nor-13-                                                          trans-prostenoic acid                                   443     326           9-oxo-15-hydroxy-3-oxa-                                                       19,20-dinor-13-trans,-                                                        17-prostadienoic acid                                   444     327           9-oxo-15-hydroxy-7,19,-                                                       20-trinor-13-trans,17-                                                        prostadienoic acid                                      445     328           9-oxo-15-hydroxy-7-nor-                                                       18,19-dimethyl-13-                                                            trans,18-prostadienoic                                                        acid                                                    446     329           9-oxo-15-hydroxy-7,18,-                                                       19,20-tetranor-16-meth-                                                       yl-13-trans-prostenoic                                                        acid                                                    447     330           9-oxo-15-hydroxy-2-                                                           fluoro-20-nor-13-trans-                                                       prostenoic acid                                         448     331           9-oxo-15-hydroxy-2-                                                           fluoro-20-ethyl-13-                                                           trans-prostenoic acid                                   449     332           9-oxo-15-hydroxy-2-                                                           fluoro-16-ethyl-19,20-                                                        dinor-13-trans-pros-                                                          tenoic acid                                             450     333           9-oxo-15-hydroxy-2-                                                           fluoro-16-methyl-20-                                                          nor-13-trans-pros-                                                            tenoic acid                                             451     334           9-oxo-15-hydroxy-2-                                                           fluoro-19-methyl-13-                                                          trans,18-prostadienoic                                                        acid                                                    452     335           9-oxo-15-hydroxy-7a-                                                          homo-18,19-dimethyl-                                                          13-trans,18-prosta-                                                           dienoic acid                                            453     336           9-oxo-15-hydroxy-7a-                                                          homo-19,20-dinor-13-                                                          trans,17-prostadienoic                                                        acid                                                    454     337           9-oxo-15-hydroxy-2-                                                           phenyl-20-nor-13-trans-                                                       prostenoic acid                                         455     338           9-oxo-15-hydroxy-2-                                                           phenyl-20-ethyl-13-                                                           trans-prostenoic acid                                   456     339           9-oxo-15-hydroxy-2-                                                           phenyl-16-ethyl-13-                                                           trans-prostenoic acid                                   457     340           9-oxo-15-hydroxy-2-phen-                                                      yl-16-methyl-18,19,20-                                                        trinor-13-trans-pros-                                                         tenoic acid                                             458     341           9-oxo-15-hydroxy-2-                                                           phenyl-18,19-dimethyl-                                                        13-trans,18-prosta-                                                           dienoic acid                                            459     342           9-oxo-15-hydroxy-2-                                                           methyl-20-nor-13-trans-                                                       prostenoic acid                                         460     343           9-oxo-15-hydroxy-2,20-                                                        dimethyl-13-trans-                                                            prostenoic acid                                         461     344           9-oxo-15-hydroxy-2-                                                           methyl-16-ethyl-19,20-                                                        dinor-13-trans-pros-                                                          tenoic acid                                             462     345           9-oxo-15-hydroxy-2,19-                                                        dimethyl-13-trans,18-                                                         prostadienoic acid                                      463     346           9-oxo-15-hydroxy-2-                                                           methyl-19,20-dinor-                                                           13-trans,17-prosta-                                                           dienoic acid                                            464     347           9-oxo-15-hydroxy-10a-                                                         homo-20-nor-13-trans-                                                         prostenoic acid                                         465     348           9-oxo-15-hydroxy-10a-                                                         homo-20-methyl-13-                                                            trans-prostenoic acid                                   466     349           9-oxo-15-hydroxy-10a-                                                         homo-16-ethyl-13-trans-                                                       prostenoic acid                                         467     350           9-oxo-15-hydroxy-10a-                                                         homo-18,19-dimethyl-                                                          13-trans,18-prosta-                                                           dienoic acid                                            468     351           9-oxo-15-hydroxy-10a-                                                         homo-19,20-dinor-13-                                                          trans,17-prostadienoic                                                        acid                                                    469     352           9-oxo-15-hydroxy-10a-                                                         homo-5,6,7-trinor-20-                                                         ethyl-13-trans-pros-                                                          tenoic acid                                             470     353           9-oxo-15-hydroxy-10a-                                                         homo-5,6,7,20-tetra-                                                          nor-16-methyl-13-trans-                                                       prostenoic acid                                         471     354           9-oxo-15-hydroxy-10a-                                                         homo-5,6,7-trinor-19-                                                         isobutyl-13-trans,18-                                                         prostadienoic acid                                      472     355           9-oxo-15-hydroxy-10a-                                                         homo-20-methyl-13-                                                            trans-prostenoic acid                                   473     356           9-oxo-15-hydroxy-10a-                                                         homo-19-methyl-13-                                                            trans,18-prostadienoic                                                        acid                                                    474     357           9-oxo-15-hydroxy-7a,10a-                                                      bishomo-20-nor-13-                                                            trans-prostenoic acid                                   475     358           9-oxo-15-hydroxy-7a,10a-                                                      bishomo-20-ethyl-13-                                                          trans-prostenoic acid                                   476     359           9-oxo-15-hydroxy-7a,10a-                                                      bishomo-16-methyl-20-                                                         nor-13-trans-prostenoic                                                       acid                                                    477     360           9-oxo-15-hydroxy-7a,10a-                                                      bishomo-19-methyl-13-                                                         trans,18-prostadienoic                                                        acid                                                    478     361           9-oxo-15-hydroxy-3-thia-                                                      20-nor-13-trans-pros-                                                         tenoic acid                                             479     362           9-oxo-15-hydroxy-3-thia-                                                      20-methyl-13-trans-                                                           prostenoic acid                                         480     363           9-oxo-15-hydroxy-3-thia-                                                      16-ethyl-13-trans-                                                            prostenoic acid                                         481     364           9-oxo-15-hydroxy-3-thia-                                                      16-methyl-18,19,20-                                                           trinor-13-trans-pros-                                                         tenoic acid                                             482     365           9-oxo-15-hydroxy-3-thia-                                                      19-methyl-13-trans,18-                                                        prostadienoic acid                                      483     366           9-oxo-15-hydroxy-3-thia-                                                      19,20-dinor-13-trans,-                                                        17-prostadienoic acid                                   484     367           9-oxo-15-hydroxy-20-nor-                                                      5-cis,13-trans-prosta-                                                        dienoic acid                                            485     368           9-oxo-15-hydroxy-20-                                                          methyl-5-cis,13-trans-                                                        prostadienoic acid                                      486     369           9-oxo-15-hydroxy-16-                                                          ethyl-5-cis,13-trans-                                                         prostadienoic acid                                      487     370           9-oxo-15-hydroxy-16-                                                          methyl-20-nor-5-cis,13-                                                       trans-prostadienoic                                                           acid                                                    488     371           9-oxo-15-hydroxy-19-                                                          methyl-5-cis,13-trans,-                                                       18-prostatrienoic acid                                  489     372           9-oxo-15-hydroxy-18,19-                                                       dimethyl-5-cis,13-                                                            trans-18-prostatrienoic                                                       acid                                                    490     373           9-oxo-15-hydroxy-19,20-                                                       dinor-5-cis,13-trans,-                                                        17-prostatrienoic acid                                  491     374           9-oxo-15-hydroxy-5-cis,-                                                      13-trans,17-cis-prosta-                                                       trienoic acid                                           ______________________________________                                    

EXAMPLE 492 Preparation of 3-(tert-butoxy)-1-iodooctane

Into a solution of 16.7 g. of 1-iodo-3-octanol [Shriner et al., J. Org.Chem. 4, 103 (1939)] in 250 ml. of methylene chloride is bubbledisobutylene at a fast rate until the solution is saturated. The solutionis cooled and 2 ml. of concentrated sulfuric acid is added. The solutionis stoppered and allowed to stand at room temperature for 3 days. Afterthe solution is poured into 300 ml. of 5% sodium carbonate, the organicphase is separated, washed with brine, dried with anhydrous magnesiumsulfate and evaporated to dryness. Distillation gave 13.9 g. (68%) ofproduct, b.p. 50° C. (0.008 nm).

EXAMPLE 493 Preparation of 15-(tert-butoxy)-9-oxoprostanoic acid, ethylester

To a Grignard solution, prepared from 5.05 g. of magnesium and 65.8 g.of 3-(tert-butoxy)-1-iodooctane in 150 ml. of diethyl ether undernitrogen atmosphere, is added 4.0 g. of copperiodide-tri-n-butylphosphine complex followed by dropwise addition of 49g. of 2-(6-carbethoxyhexyl)cyclopent-2-en-1-one [Hardegger et al., Helv.Chim. Acta 50, 2501 (1967)] and the resulting mixture is stirred for 18hours. Saturated ammonium chloride (110 ml.) is added followed by 100ml. of water and 100 ml. of diethyl ether. Unreacted magnesium isremoved by filtration. The ethereal layer is washed successively withaqueous sodium thiosulfate solution, ammonium chloride solution, andwater, dried over magnesium sulfate and taken to dryness to give an oil.Distillation at 0.05 mm. (bath 100°-185° C.) gives 45.4 g. of materialcontaining unreacted starting material and 30 g. (85% yield based onnon-recovered starting material; see below) of residue which containsthe desired product. This material is chromatographed on silica gel. Theproduct is eluted with diethyl ether to give 25.2 g. (71% based onrecovered starting material) of a syrup; this material has nosignificant ultraviolet absorption; λ_(max) ^(KBr) 5.74, 7.20, 7.35,8.35μ; nmr 2H quartet δ4.09 (OCH₂ of ester), 1H broad singlet 3.57(carbinolic proton), 5H overlapping multiplets 2.0-2.4 (protons next toC-O), 3H triplet 1.22 (CH₃ of ethyl), OH singlet 1.17 (CH₂ 's tot-butyl) and 3H triplet 0.9 (terminal methyl); mass spectrum: m/e 424.

EXAMPLE 494

Preparation of 15-hydroxy-9-oxoprostanoic acid, ethyl ester

A solution of 25 g. of 15-(tert-butoxy)-9-oxoprostanoic acid, ethylester in 100 ml. of trifluoroacetic acid is stirred in an ice bath for 1hour and is then poured into 500 ml. of ice water and extracted severaltimes with chloroform. The combined chloroform extracts are washed withsaturated sodium bicarbonate solution, saturated sodium chloridesolution, dried with anhydrous magnesium sulfate, and taken to dryness.The resulting oil is dissolved in 200 ml. of 1 N ammonium hydroxide inethanol, kept at ambient temperature for 15 minutes, then taken todryness. The residual oil is dissolved in chloroform and washed with 1 Nhydrochloric acid, saturated sodium chloride solution, dried and takento dryness to give 21.7 g. (100%) of product as a yellow syrup. There isessentially no uv absorption; λ_(max) ^(KBR) 2.90, 5.75, 8.45μ; nmr 2Hquartet δ4.13 (OCH₂ of ester), 1H broad singlet 3.63 (carbinolicproton), 3H triplet (CH₃ of ester), and 3H distorted triplet 0.92(terminal methyl); mass spectrum: m/e 368.

EXAMPLE 495 Preparation of 15-hydroxy-9-oxoprostanoic acid

A suspension of 15 g. of 15-hydroxy-9-oxoprostanoic acid, ethyl ester in230 ml. of aqueous methanol (1:1) containing 6.45 g. of potassiumhydroxide is stirred at 50° C. for 1 hour and then at room temperaturefor 18 hours. The resulting solution is acidified with 1H hydrochloricacid, saturated with sodium chloride, and extracted several times withdiethyl ether. The combined ether extracts are washed twice withsaturated sodium chloride solution, dried with anhydrous magnesiumsulfate, and taken to dryness to give 13.1 g. (94%) of product as anoil. There is essentially no uv absorption; [α]_(D) ²⁵ 0° (1.0% inCHCl₃); λ_(max) ^(KBr) 2.80-3.70 (broad), 5.75, 5.87μ; nmr 2H singletδ6.65 (hydroxyl and carboxyl protons), 1H broad singlet (3.63(carbinolic proton), and 3H distorted triplet 0.93 (terminal methyl);mass spectrum: m/e 340.

EXAMPLE 496 Preparation of 1-chloro-3-hydroxy-4-octyne

To 68 ml. of 1.6 M butyllithium in hexane at -50° C. is added dropwise,with stirring, 7.4 g. of 1-pentyne. The resulting white sludge isdiluted with 20 ml. of hexane, brought to 10° C. and treated with 11 g.of freshly prepared β-chloropropionaldehyde (Org. Syn., Coll. Vol. I, p.166) at such a rate that the temperature is maintained at 10°-15° C. Thesolution is allowed to stir at ambient temperature for 18 hours thentreated with saturated ammonium chloride solution. The organic phase isseparated, washed with dilute hydrochloric solution, dried withanhydrous magnesium sulfate and taken to dryness. Distillation gives 5.1g. of product b.p. 65°-66° C. at 0.3 nm.; λmax. 2.95 (--OH) and 4.55μ(--C.tbd.C--); vapor phase chromatography shows one peak.

EXAMPLE 497 Preparation of 1-chloro-3-hydroxy-4-cis-octene

A solution of 2 g. of 1-chloro-3-hydroxy-4-octyne (Example 496) ishydrogenated in 50 ml. absolute alcohol using 200 mg. of Lindlarcatalyst (5% Pd on CaCO₃). The catalyst is removed by filtration and themother liquor is taken to dryness to give 2 g. of an oil; λmax. 2.95(--OH) and 7.25μ ##STR37##

EXAMPLE 498 Preparation of 3-hydroxy-1-iodo-4-octyne

A mixture of 15 g. of sodium iodide in 100 ml. of 2-butanone is stirredat the reflux temperature for 30 minutes. To the cooled mixture is added12 g. of 1-chloro-3-hydroxy-4-octyne in 150 ml. of 2-butanone. Theresulting mixture is stirred at the reflux temperature for 18 hours thencooled and filtered. The mother liquor is taken to dryness and theresidue is triturated with benzene and filtered. The benzene is taken todryness to give the subject product as an oil. The material is shown tobe homogeneous by vapor phase chromatography and thin layerchromatography.

EXAMPLE 499 Preparation of 3-hydroxy-1-iodo-4-cis-octen

The subject compound is prepared from 3-hydroxy-1-chloro-4-cis-octeneand sodium iodide by the method of Example 498.

EXAMPLE 500 Preparation of 3-t-butoxy-1-iodo-4-octyne

The subject compound is prepared from 3-hydroxy-1-iodo-4-octyne (Example498) and isobutylene by the method of Example 492.

EXAMPLE 501 Preparation of 3-t-butoxy-1-iodo-4-cis-octene

The subject compound is prepared from 3-hydroxy-1-iodo-4-cis-octene(Example 499) and isobutylene by the method of Example 492.

EXAMPLE 502 Preparation of 3-(tert-butoxy)-1-iodohexane

A mixture of 23.4 g. of 1-chloro-3-hexanol [Fourneau, et. al., Bull.Soc. Chem. France, 25, 367 (1919)] in 300 ml. of 2-butanone containing30 g. of sodium iodide is stirred at the reflux temperature for 18hours. The cooled solution is filtered and the mother liquor is taken todryness. Distillation of the residue affords 32.9 g. (84%) of1-iodo-3-hexanol, b.p. 105° C. (10 mm). Treatment of this material in500 ml. of methylene chloride, containing 4 ml. of concentrated sulfuricacid, with isobutylene according to the procedure described in Example492 gives 27 g. of crude material. Chromatography on florisil affords 16g. of product; λmax. 7.22 and 7.37μ (tert-butyl group).

EXAMPLES 503-558

Treatment of the cyclopentenones designated in the table below with thedesignated Grignard reagents by the procedure of Example 493 isproductive of the alkyl 9-oxo-15-t-butoxy-8ξ-prostanoates andprostenoates of the table. 3-t-Butoxyoctylmagnesium iodide was preparedfrom 3-t-butoxy-1-iodooctane (Example 492); 3-t-butoxyhexyl magnesiumiodide was prepared from 3-t-butoxy-1-iodohexane (Example 502),3-t-butoxy-4-octynyl magnesium iodide was prepared from3-t-butoxy-1-iodo-4-octyne (Example 500); and 3-t-butoxy-4-cis-octenylmagnesium iodide was prepared from 3-t-butoxy-1-iodo-4-cis-octene(Example 501).

                                      TABLE 6                                     __________________________________________________________________________          Starting cyclopentenone                                                                            Product Alkyl 9-Oxo-15-t-butoxy-8ξ-prostanoa                               tes,                                               Example                                                                            of Example  Grignard Reagent                                                                        prostynoates and prostenoates                      __________________________________________________________________________    503  31          3-t-butoxyoctyl                                                                         ethyl 9-oxo-15-t-butoxy-2-ethyl-8ξ-prostanoa                               te                                                                  magnesium iodide                                             504  41          3-t-butoxyoctyl                                                                         ethyl 9-oxo-15-t-butoxy-3,3-dimethyl-8ξ-                         magnesium iodide                                                                        prostanoate                                        505  46          3-t-butoxyoctyl                                                                         ethyl 9-oxo-15-t-butoxy-3-oxa-8ξ-prostanoate                     magnesium iodide                                             506  70          3-t-butoxyoctyl                                                                         ethyl 9-oxo-15-t-butoxy-2-fluoro-8ξ-prostano                               ate                                                                 magnesium iodide                                             507  79          3-t-butoxyoctyl                                                                         ethyl 9-oxo-15-t-butoxy-2-phenyl-8ξ-prostano                               ate                                                                 magnesium iodide                                             508  99          3-t-butoxyoctyl                                                                         ethyl 9-oxo-15-t-butoxy-2-methyl-8ξ-prostano                               ate                                                                 magnesium iodide                                             509  118         3-t-butoxyoctyl                                                                         ethyl 9-oxo-15-t-butoxy-3-thia-8ξ-prostanoat                               e                                                                   magnesium iodide                                             510  900         3-t-butoxyoctyl                                                                         methyl 9-oxo-15-t-butoxy-8ξ-5-cis-prostenoat                               e                                                                   magnesium iodide                                             511  31          3-t-butoxyhexyl                                                                         ethyl 9-oxo-15-t-butoxy-2-ethyl-19,20-dinor-8.x                               i.-                                                                 magnesium iodide                                                                        prostanoate                                        512  41          3-t-butoxyhexyl                                                                         ethyl 9-oxo-15-t-butoxy-3,3-dimethyl-19,20-                         magnesium iodide                                                                        dinor-8ξ-prostanoate                            513  46          3-t-butoxyhexyl                                                                         ethyl 9-oxo-15-t-butoxy-3-oxa-19,20-dinor-8ξ                               -                                                                   magnesium iodide                                                                        prostanoate                                        514  70          3-t-butoxyhexyl                                                                         ethyl 9-oxo-15-t-butoxy-2-fluoro-19,20-dinor-8.                               xi.-                                                                magnesium iodide                                                                        prostanoate                                        515  79          3-t-butoxyhexyl                                                                         ethyl 9-oxo-15-t-butoxy-2-phenyl-19,20-dinor-8.                               xi.-                                                                magnesium iodide                                                                        prostanoate                                        516  99          3-t-butoxyhexyl                                                                         ethyl 9-oxo-15-t-butoxy-2-methyl-19,20-dinor-8.                               xi.-                                                                magnesium iodide                                                                        prostanoate                                        517  118         3-t-butoxyhexyl                                                                         ethyl 9-oxo-15-t-butoxy-3-thia-19,20-dinor-8.xi                               .-                                                                  magnesium iodide                                                                        prostanoate                                        518  900         3-t-butoxyhexyl                                                                         methyl 9-oxo-15-t-butoxy-19,20-dinor-8ξ-5-ci                               s-                                                                  magnesium iodide                                                                        prostenoate                                        519  13          3-t-butoxy-4-oct-                                                                       ethyl 9-oxo-15-t-butoxy-8ξ-16-prostynoate                        ynyl magnesium                                                                iodide                                                       520  15          3-t-butoxy-4-oct-                                                                       ethyl 9-oxo-15-t-butoxy-6,7-dinor-8ξ-16-                         ynyl magnesium                                                                          prostynoate                                                         iodide                                                       521  23          3-t-butoxy-4-oct-                                                                       ethyl 9-oxo-15-t-butoxy-7a,7b-bishomo-8ξ-16-                     ynyl magnesium                                                                          prostynoate                                                         iodide                                                       522  31          3-t-butoxy-4-oct-                                                                       ethyl 9-oxo-15-t-butoxy-2-ethyl-8ξ-16-prosty                               noate                                                               ynyl magnesium                                                                iodide                                                       523  41          3-t-butoxy-4-oct-                                                                       ethyl 9-oxo-15-t-butoxy-3,3-dimethyl-8ξ-16-                                O                                                                   ynyl magnesium                                                                          prostynoate                                                         iodide                                                       524  46          3-t-butoxy-4-oct-                                                                       ethyl 9-oxo-15-t-butoxy-3-oxa-8ξ-16-prostyno                               ate                                                                 ynyl magnesium                                                                iodide                                                       525  53          3-t-butoxy-4-oct-                                                                       ethyl 9-oxo-15-t-butoxy-7-nor-8ξ-16-prostyno                               ate                                                                 ynyl magnesium                                                                iodide                                                       526  70          3-t-butoxy-4-oct-                                                                       ethyl 9-oxo-15-t-butoxy-2-fluoro-8ξ-16-prost                               ynoate                                                              ynyl magnesium                                                                iodide                                                       527  74          3-t-butoxy-4-oct-                                                                       ethyl 9-oxo-15-t-butoxy-7a-homo-8ξ-16-prosty                               noate                                                               ynyl magnesium                                                                iodide                                                       528  79          3-t-butoxy-4-oct-                                                                       ethyl 9-oxo-15-t-butoxy-2-phenyl-8ξ-16-prost                               ynoate                                                              ynyl magnesium                                                                iodide                                                       529  81          3-t-butoxy-4-oct-                                                                       butyl 9-oxo-15-t-butoxy-8ξ-16-prostynoate                        ynyl magnesium                                                                iodide                                                       530  82          3-t-butoxy-4-oct-                                                                       isopropyl 9-oxo-15-t-butoxy-8ξ-16-prostynoat                               e                                                                   ynyl magnesium                                                                iodide                                                       531  83          3-t-butoxy-4-oct-                                                                       methyl 9-oxo-15-t-butoxy-8ξ-16-prostynoate                       ynyl magnesium                                                                iodide                                                       532  84          3-t-butoxy-4-oct-                                                                       decyl 9-oxo-15-t-butoxy-8ξ-16-prostynoate                        ynyl magnesium                                                                iodide                                                       533  99          3-t-butoxy-4-oct-                                                                       ethyl 9-oxo-15-t-butoxy-2-methyl-8ξ-16-prost                               ynoate                                                              ynyl magnesium                                                                iodide                                                       534  118         3-t-butoxy-4-oct-                                                                       ethyl 9-oxo-15-t-butoxy-3-thia-8ξ-16-prostyn                               oate                                                                ynyl magnesium                                                                iodide                                                       535  111         3-t-butoxy-4-oct-                                                                       ethyl 9-oxo-15-t-butoxy-10a-homo-8ξ-16-prost                               ynoate                                                              ynyl magnesium                                                                iodide                                                       536  113         3-t-butoxy-4-oct-                                                                       ethyl 9-oxo-15-t-butoxy-10a-homo-7-nor-8ξ-16                               -                                                                   ynyl magnesium                                                                          prostynoate                                                         iodide                                                       537  114         3-t-butoxy-4-oct-                                                                       ethyl 9-oxo-15-t-butoxy-7a,10a-bishomo-8ξ-16                               -                                                                   ynyl magnesium                                                                          prostynoate                                                         iodide                                                       538  900         3-t-butoxy-4-oct-                                                                       methyl 9-oxo-15-t-butoxy-8ξ-16-yne-5-cis-                        ynyl magnesium                                                                          prostenoate                                                         iodide                                                       539  13          3-t-butoxy-4-cis-                                                                       ethyl 9-oxo-15-t-butoxy-8ξ-16-cis-prostenoat                               e                                                                   octenyl magnesium                                                             iodide                                                       540  15          3-t-butoxy-4-cis-                                                                       ethyl 9-oxo-15-t-butoxy-6,7-dinor-8ξ-16-cis-                               N                                                                   octenyl magnesium                                                                       prostenoate                                                         iodide                                                       541  23          3-t-butoxy-4-cis-                                                                       ethyl 9-oxo-15-t-butoxy-7a,7b-bishomo-8ξ-16-                               O                                                                   octenyl magnesium                                                                       cis-prostenoate                                                     iodide                                                       542  31          3-t-butoxy-4-cis-                                                                       ethyl 9-oxo-15-t-butoxy-2-ethyl-8ξ-16-cis-                       octenyl magnesium                                                                       prostenoate                                                         iodide                                                       543  41          3-t-butoxy-4-cis-                                                                       ethyl 9-oxo-15-t-butoxy-3,3-dimethyl-8ξ-16-c                               is-                                                                 octenyl magnesium                                                                       prostenoate                                                         iodide                                                       544  46          3-t-butoxy-4-cis-                                                                       ethyl 9-oxo-15-t-butoxy-3-oxa-8ξ-16-cis-                         octenyl magnesium                                                                       prostenoate                                                         iodide                                                       545  53          3-t-butoxy-4-cis-                                                                       ethyl 9-oxo-15-t-butoxy-7-nor-8ξ-16-cis-                         octenyl magnesium                                                                       prostenoate                                                         iodide                                                       546  70          3-t-butoxy-4-cis-                                                                       ethyl 9-oxo-15-t-butoxy-2-fluoro-8ξ-16-cis-                      octenyl magnesium                                                                       prostenoate                                                         iodide                                                       547  74          3-t-butoxy-4-cis-                                                                       ethyl 9-oxo-15-t-butoxy-7a-homo-8ξ-16-cis-                       octenyl magnesium                                                                       prostenoate                                                         iodide                                                       548  79          3-t-butoxy-4-cis-                                                                       ethyl 9-oxo-15-t-butoxy-2-phenyl-8ξ-16-cis-                      octenyl magnesium                                                                       prostenoate                                                         iodide                                                       549  81          3-t-butoxy-4-cis-                                                                       butyl 9-oxo-15-t-butoxy-8ξ-16-cis-prostenoat                               e                                                                   octenyl magnesium                                                             iodide                                                       550  82          3-t-butoxy-4-cis-                                                                       isopropyl 9-oxo-15-t-butoxy-8ξ-16-cis-                           octenyl magnesium                                                                       prostenoate                                                         iodide                                                       551  83          3-t-butoxy-4-cis-                                                                       methyl 9-oxo-15-t-butoxy-8ξ-16-cis-                              octenyl magnesium                                                                       prostenoate                                                         iodide                                                       552  84          3-t-butoxy-4-cis-                                                                       decyl 9-oxo-15-t-butoxy-8ξ-16-cis-prostenoat                               e                                                                   octenyl magnesium                                                             iodide                                                       553  99          3-t-butoxy-4-cis-                                                                       ethyl 9-oxo-15-t-butoxy-2-methyl-8ξ-16-cis-                                N                                                                   octenyl magnesium                                                                       prostenoate                                                         iodide                                                       554  118         3-t-butoxy-4-cis-                                                                       ethyl 9-oxo-15-t-butoxy-3-thia-8ξ-16-cis-                        octenyl magnesium                                                                       prostenoate                                                         iodide                                                       555  111         3-t-butoxy-4-cis-                                                                       ethyl 9-oxo-15-t-butoxy-10a-homo-8ξ-16-cis-                                O                                                                   octenyl magnesium                                                                       prostenoate                                                         iodide                                                       556  113         3-t-butoxy-4-cis-                                                                       ethyl 9-oxo-15-t-butoxy-10a-homo-7-nor-8ξ-16                               -                                                                   octenyl magnesium                                                                       cis-prostenoate                                                     iodide                                                       557  114         3-t-butoxy-4-cis-                                                                       ethyl 9-oxo-15-t-butoxy-7a,10a-bishomo-8ξ-16                               -                                                                   octenyl magnesium                                                                       cis-prostenoate                                                     iodide                                                       558  900         3-t-butoxy-4-cis-                                                                       methyl 9-oxo-15-t-butoxy-8ξ-5-cis-16-cis-                        octenyl magnesium                                                                       prostadienoate                                                      iodide                                                       __________________________________________________________________________

EXAMPLES 599-614

Treatment of the 9-oxo-15-t-butoxy derivatives designated in the tablebelow with trifluoroacetic acid and then with aqueous ammonia by themethod described in Example 494 is productive of the 9-oxo-15-hydroxyesters of the table.

                  TABLE 7                                                         ______________________________________                                                Starting 15-t-                                                        Ex-     butoxy derivative                                                                            Product Alkyl 9-oxo-15-                                ample   of Example     hydroxy derivative                                     ______________________________________                                        559     503            Ethyl 9-oxo-15-hydroxy-                                                       2-ethyl-prostanoate                                    560     504            Ethyl 9-oxo-15-hydroxy-                                                       3,3-dimethyl-prostano-                                                        ate                                                    561     505            Ethyl 9-oxo-15-hydroxy-                                                       3-oxa-prostanoate                                      562     506            Ethyl 9-oxo-15-hydroxy-                                                       2-fluoro-prostanoate                                   563     507            Ethyl 9-oxo-15-hydroxy-                                                       2-phenyl-prostanoate                                   564     508            Ethyl 9-oxo-15-hydroxy-                                                       2-methyl-prostanoate                                   565     509            Ethyl 9-oxo-15-hydroxy-                                                       3-thia-prostanoate                                     566     510            Methyl 9-oxo-15-hydroxy-                                                      5-cis-prostenoate                                      567     511            Ethyl 9-oxo-15-hydroxy-                                                       2-ethyl-19,20-dinor-                                                          prostanoate                                            568     512            Ethyl 9-oxo-15-hydroxy-                                                       3,3-dimethyl-19,20-                                                           dinor-prostanoate                                      569     513            Ethyl 9-oxo-15-hydroxy-                                                       3-oxa-19,20-dinor-                                                            prostanoate                                            570     514            Ethyl 9-oxo-15-hydroxy-                                                       2-fluoro-19,20-dinor-                                                         prostanoate                                            571     515            Ethyl 9-oxo-15-hydroxy-                                                       2-phenyl-19,20-dinor-                                                         prostanoate                                            572     516            Ethyl 9-oxo-15-hydroxy-                                                       2-methyl-19,20-dinor-                                                         prostanoate                                            573     517            Ethyl 9-oxo-15-hydroxy-                                                       3-thia-19,20-dinor-                                                           prostanoate                                            574     518            Methyl 9-oxo-15-hydroxy-                                                      19,20-dinor-5-cis-                                                            prostenoate                                            575     519            Ethyl 9-oxo-15-hydroxy-                                                       16-prostynoate                                         576     520            Ethyl 9-oxo-15-hydroxy-                                                       6,7-dinor-16-prostyno-                                                        ate                                                    577     521            Ethyl 9-oxo-15-hydroxy-                                                       7a,7b-bishomo-16-prost-                                                       ynoate                                                 578     522            Ethyl 9-oxo-15-hydroxy-                                                       2-ethyl-16-prostynoate                                 579     523            Ethyl 9-oxo-15-hydroxy-                                                       3,3-dimethyl-16-prost-                                                        ynoate                                                 580     524            Ethyl 9-oxo-15-hydroxy-                                                       3-oxa-16-prostynoate                                   581     525            Ethyl 9-oxo-15-hydroxy-                                                       7-nor-16-prostynoate                                   582     526            Ethyl 9-oxo-15-hydroxy-                                                       2-fluoro-16-prostynoate                                583     527            Ethyl 9-oxo-15-hydroxy-                                                       7a-homo-16-prostynoate                                 584     528            Ethyl 9-oxo-15-hydroxy-                                                       2-phenyl-16-prostynoate                                585     529            Butyl 9-oxo-15-hydroxy-                                                       16-prostynoate                                         586     530            Isopropyl 9-oxo-15-hy-                                                        droxy-16-prostynoate                                   587     531            Methyl 9-oxo-15-hydroxy-                                                      16-prostynoate                                         588     532            Decyl 9-oxo-15-hydroxy-                                                       16-prostynoate                                         589     533            Ethyl 9-oxo-15-hydroxy-                                                       2-methyl-16-prostynoate                                590     534            Ethyl 9-oxo-15-hydroxy-                                                       3-thia-16-prostynoate                                  591     535            Ethyl 9-oxo-15-hydroxy-                                                       10a-homo-16-prostynoate                                592     536            Ethyl 9-oxo-15-hydroxy-                                                       10a-homo-7-nor-16-                                                            prostynoate                                            593     537            Ethyl 9-oxo-15-hydroxy-                                                       7a,10a-bishomo-16-                                                            prostynoate                                            594     538            Methyl 9-oxo-15-hydroxy-                                                      16-yne-5-cis-prostenoate                               595     539            Ethyl 9-oxo-15-hydroxy-                                                       16-cis-prostenoate                                     596     540            Ethyl 9-oxo-15-hydroxy-                                                       6,7-dinor-16-cis-pros-                                                        tenoate                                                597     541            Ethyl 9-oxo-15-hydroxy-                                                       7a,7b-bishomo-16-cis-                                                         prostenoate                                            598     542            Ethyl 9-oxo-15-hydroxy-                                                       2-ethyl-16-cis-prosteno-                                                      ate                                                    599     543            Ethyl 9-oxo-15-hydroxy-                                                       3,3-dimethyl-16-cis-                                                          prostenoate                                            600     544            Ethyl 9-oxo-15-hydroxy-                                                       3-oxa-16-cis-prostenoate                               601     545            Ethyl 9-oxo-15-hydroxy-                                                       7-nor-16-cis-prostenoate                               602     546            Ethyl 9-oxo-15-hydroxy-                                                       2-fluoro-16-cis-prosten-                                                      oate                                                   603     547            Ethyl 9-oxo-15-hydroxy-                                                       7a-homo-16-cis-prosten-                                                       oate                                                   604     548            Ethyl 9-oxo-15-hydroxy-                                                       2-phenyl-16-cis-prosten-                                                      oate                                                   605     549            Butyl 9-oxo-15-hydroxy-                                                       16-cis-prostenoate                                     606     550            Isopropyl 9-oxo-15-hy-                                                        droxy-16-cis-prostenoate                               607     551            Methyl 9-oxo-15-hydroxy-                                                      16-cis-prostenoate                                     608     552            Decyl 9-oxo-15-hydroxy-                                                       16-cis-prostenoate                                     609     553            Ethyl 9-oxo-15-hydroxy-                                                       2-methyl-16-cis-pros-                                                         tenoate                                                610     554            Ethyl 9-oxo-15-hydroxy-                                                       3-thia-16-cis-prosteno-                                                       ate                                                    611     555            Ethyl 9-oxo-15-hydroxy-                                                       10a-homo-16-cis-pros-                                                         tenoate                                                612     556            Ethyl 9-oxo-15-hydroxy-                                                       10a-homo-7-nor-16-cis-                                                        prostenoate                                            613     557            Ethyl 9-oxo-15-hydroxy-                                                       7a,10a-bishomo-16-cis-                                                        prostenoate                                            614     558            Methyl 9-oxo-15-hydroxy-                                                      5-cis-16-cis-prostadi-                                                        enoate                                                 ______________________________________                                    

EXAMPLES 615-662

Saponification of the 9-oxo-15-hydroxy alkyl esters designated in thetable below by the procedure described in Example 495 is productive ofthe carboxylic acids of the table.

                  TABLE 8                                                         ______________________________________                                                Starting alkyl                                                        Ex-     ester of     Product 9-oxo-15-hydroxy-                                ample   Example      prostanoic acid                                          ______________________________________                                        615     559          9-oxo-15-hydroxy-2-ethyl-                                                     prostanoic acid                                          616     560          9-oxo-15-hydroxy-3,3-di-                                                      methyl-prostanoic acid                                   617     561          9-oxo-15-hydroxy-3-oxa-                                                       prostanoic acid                                          618     562          9-oxo-15-hydroxy-2-fluoro-                                                    prostanoic acid                                          619     563          9-oxo-15-hydroxy-2-phenyl-                                                    prostanoic acid                                          620     564          9-oxo-15-hydroxy-2-methyl-                                                    prostanoic acid                                          621     565          9-oxo-15-hydroxy-3-thia-                                                      prostanoic acid                                          622     566          9-oxo-15-hydroxy-5-cis-                                                       prostenoic acid                                          623     567          9-oxo-15-hydroxy-2-ethyl-                                                     19,20-dinor-prostanoic                                                        acid                                                     624     568          9-oxo-15-3,3-dimethyl-19,                                                     20-dinor-prostanoic acid                                 625     569          9-oxo-15-hydroxy-3-oxa-                                                       19,20-dinor-prostanoic                                                        acid                                                     626     570          9-oxo-15-hydroxy-2-fluoro-                                                    19,20-dinor-prostanoic                                                        acid                                                     627     571          9-oxo-15-hydroxy-2-phenyl-                                                    19,20-dinor-prostanoic                                                        acid                                                     628     572          9-oxo-15-hydroxy-2-methyl-                                                    19,20-dinor-prostanoic                                                        acid                                                     629     573          9-oxo-15-hydroxy-3-thia-                                                      19,20-dinor-prostanoic                                                        acid                                                     630     574          9-oxo-15-hydroxy-19,20-                                                       dinor-5-cis-prostenoic acid                              631     575          9-oxo-15-hydroxy-16-pros-                                                     tynoic acid                                              632     576          9-oxo-15-hydroxy-6,7-dinor-                                                   16-prostynoic acid                                       633     577          9-oxo-15-hydroxy-7a,7b-bis-                                                   homo-16-prostynoic acid                                  634     578          9-oxo-15-hydroxy-2-ethyl-                                                     16-prostynoic acid                                       635     579          9-oxo-15-hydroxy-3,3-di-                                                      methyl-16-prostynoic acid                                636     580          9-oxo-15-hydroxy-3-oxa-16-                                                    prostynoic acid                                          637     581          9-oxo-15-hydroxy-7-nor-16-                                                    prostynoic acid                                          638     582          9-oxo-15-hydroxy-2-fluoro-                                                    16-prostynoic acid                                       639     583          9-oxo-15-hydroxy-7a-homo-                                                     16-prostynoic acid                                       640     584          9-oxo-15-hydroxy-2-phenyl-                                                    16-prostynoic acid                                       641     589          9-oxo-15-hydroxy-2-methyl-                                                    16-prostynoic acid                                       642     590          9-oxo-15-hydroxy-3-thia-                                                      16-prostynoic acid                                       643     591          9-oxo-15-hydroxy-10a-homo-                                                    16-prostynoic acid                                       644     592          9-oxo-15-hydroxy-10a-homo-                                                    7-nor-16-prostynoic acid                                 645     593          9-oxo-15-hydroxy-7a,10a-                                                      bishomo-16-prostynoic acid                               646     594          9-oxo-15-hydroxy-16-yne-5-                                                    cis-prostenoic acid                                      647     595          9-oxo-15-hydroxy-16-cis-                                                      prostenoic acid                                          648     596          9-oxo-15-hydroxy-6,7-dinor-                                                   16-cis-prostenoic acid                                   649     597          9-oxo-15-hydroxy-7a,7b-bis-                                                   homo-16-cis-prostenoic acid                              650     598          9-oxo-15-hydroxy-2-ethyl-                                                     16-cis-prostenoic acid                                   651     599          9-oxo-15-hydroxy-3,3-di-                                                      methyl-16-cis-prostenoic                                                      acid                                                     652     600          9-oxo-15-hydroxy-3-oxa-16-                                                    cis-prostenoic acid                                      653     601          9-oxo-15-hydroxy-7-nor-16-                                                    cis-prostenoic acid                                      654     602          9-oxo-15-hydroxy-2-fluoro-                                                    16-cis-prostenoic acid                                   655     603          9-oxo-15-hydroxy-7a-homo-                                                     16-cis-prostenoic acid                                   656     604          9-oxo-15-hydroxy-2-phenyl-                                                    16-cis-prostenoic acid                                   657     609          9-oxo-15-hydroxy-2-methyl-                                                    16-cis-prostenoic acid                                   658     610          9-oxo-15-hydroxy-3-thia-                                                      16-cis-prostenoic acid                                   659     611          9-oxo-15-hydroxy-10a-homo-                                                    16-cis-prostenoic acid                                   660     612          9-oxo-15-hydroxy-10a-homo-                                                    7-nor-16-cis-prostenoic                                                       acid                                                     661     613          9-oxo-15-hydroxy-7a,10a-                                                      bishomo-16-cis-prosten-                                                       oic acid                                                 662     614          9-oxo-15-hydroxy-5-cis-                                                       16-cis-prostadienoic                                                          acid                                                     ______________________________________                                    

EXAMPLE 663 Ethyl 9-oxo-15-hydroxy-16-trans-prostenoate

To a mixture of 1 g. of ethyl 9-oxo-15-hydroxy-16-prostynoate (Example575), 11 ml. of water and 27 ml. of dimethylformamide is added 27 ml. of0.45 N chromous sulfate solution. The mixture is stirred for 48 hoursunder nitrogen atmosphere. The mixture then is extracted with etherseveral times and the combined extracts are taken to dryness. Silica gelchromatography gives the subject product as an oil.

EXAMPLES 664-682

Treatment of the 9-oxo-15-hydroxy-16-prostynoates listed in Table 8Abelow with chromous sulfate in the manner of Example 663 is productiveof the product 9-oxo-15-hydroxy-16-trans-prostenoates of the table.

                  TABLE 8A                                                        ______________________________________                                                Starting      Product                                                 Ex-     16-prostenoate                                                                              9-oxo-15-hydroxy-16-                                    ample   of Example    trans-prostenoate                                       ______________________________________                                        664     576           Ethyl 9-oxo-15-hydroxy-                                                       6,7-dinor-16-trans-                                                           prostenoate                                             665     577           Ethyl 9-oxo-15-hydroxy-                                                       7a,7b-bishomo-16-trans-                                                       prostenoate                                             666     578           Ethyl 9-oxo-15-hydroxy-                                                       2-ethyl-16-trans-pros-                                                        tenoate                                                 667     579           Ethyl 9-oxo-15-hydroxy-                                                       3,3-dimethyl-16-trans-                                                        prostenoate                                             668     580           Ethyl 9-oxo-15-hydroxy-                                                       3-oxa-16-trans-prosten-                                                       oate                                                    669     581           Ethyl 9-oxo-15-hydroxy-                                                       7-nor-16-trans-pros-                                                          tenoate                                                 670     582           Ethyl 9-oxo-15-hydroxy-                                                       2-fluoro-16-trans-pros-                                                       tenoate                                                 671     583           Ethyl 9-oxo-15-hydroxy-                                                       7a-homo-16-trans-pros-                                                        tenoate                                                 672     584           Ethyl 9-oxo-15-hydroxy-                                                       2-phenyl-16-trans-pros-                                                       tenoate                                                 673     585           Butyl 9-oxo-15-hydroxy-                                                       16-trans-prostenoate                                    674     586           Isopropyl 9-oxo-15-                                                           hydroxy-16-trans-pros-                                                        tenoate                                                 675     587           Methyl 9-oxo-15-hyroxy-                                                       16-trans-prostenoate                                    676     588           Decyl 9-oxo-15-hydroxy-                                                       16-trans-prostenoate                                    677     589           Ethyl 9-oxo-15-hydroxy-                                                       2-methyl-16-trans-pros-                                                       tenoate                                                 678     590           Ethyl 9-oxo-15-hydroxy-                                                       3-thia-16-trans-pros-                                                         tenoate                                                 679     591           Ethyl 9-oxo-15-hydroxy-                                                       10a-homo-16-trans-pros-                                                       tenoate                                                 680     592           Ethyl 9-oxo-15-hydroxy-                                                       10a-homo-7-nor-16-trans-                                                      prostenoate                                             681     593           Ethyl 9-oxo-15-hydroxy-                                                       7a,10a-bishomo-16-trans-                                                      prostenoate                                             682     594           Methyl 9-oxo-15-hydroxy-                                                      5-cis,16-trans-prosta-                                                        dienoate                                                ______________________________________                                    

EXAMPLE 683-698

Saponification of the alkyl 9-oxo-15-hydroxy-16-trans-prostenoateslisted in Table 8B below by the procedure described in Example 495 isproductive of the corresponding prostenoic acids of the table.

                  TABLE 8B                                                        ______________________________________                                                Starting      Product 9-oxo-15-                                       Ex-     alkyl ester   hydroxy-16-trans                                        ample   of Example    prostenoic acids                                        ______________________________________                                        683     663           9-oxo-15-hydroxy-16-                                                          trans-prostenoic acid                                   684     664           9-oxo-15-hydroxy-6,7-                                                         dinor-16-trans-prosten-                                                       oic acid                                                685     665           9-oxo-15-hydroxy-7a,7b-                                                       bishomo-16-trans-pros-                                                        tenoic acid                                             686     666           9-oxo-15-hydroxy-2-                                                           ethyl-16-trans-prosten-                                                       oic acid                                                687     667           9-oxo-15-hydroxy-3,3-                                                         dimethyl-16-trans-pros-                                                       tenoic acid                                             688     668           9-oxo-15-hydroxy-3-oxa-                                                       16-trans-prostenoic acid                                689     669           9-oxo-15-hydroxy-7-nor-                                                       16-trans-prostenoic acid                                690     670           9-oxo-15-hydroxy-2-                                                           fluoro-16-trans-pros-                                                         tenoic acid                                             691     671           9-oxo-15-hydroxy-7a-                                                          homo-16-trans-prostenoic                                                      acid                                                    692     672           9-oxo-15-hydroxy-2-                                                           phenyl-16-trans-pros-                                                         tenoic acid                                             693     677           9-oxo-15-hydroxy-2-meth-                                                      yl-16-trans-prostenoic                                                        acid                                                    694     678           9-oxo-15-hydroxy-3-thia-                                                      16-trans-prostenoic acid                                695     679           9-oxo-15-hydroxy-10a-                                                         homo-16-trans-prostenoic                                                      acid                                                    696     680           9-oxo-15-hydroxy-10a-                                                         homo-7-nor-16-trans-                                                          prostenoic acid                                         697     681           9-oxo-15-hydroxy-7a,10a-                                                      bishomo-16-trans-pro-                                                         stenoic acid                                            698     682           9-oxo-15-hydroxy-5-cis,                                                       16-trans-prostadienoic                                                        acid                                                    ______________________________________                                    

EXAMPLE 699 Preparation of 9-oxo-15-hydroxy-3,3-dimethylprostanoic acid

A 2 g. sample of 9-oxo-15-hydroxy-3,3-dimethyl-13-trans-prostenoic acidis hydrogenated using 700 mg. of 10 palladium on carbon in 50 ml. ofabsolute alcohol. The catalyst is removed by filtration and the motherliquor is taken to dryness to give 2 L g. of subject compound as an oil.

EXAMPLE 723 Preparation of 1-chloro-trans-1-octen-3-one

To a slurry of 233.5 g. (1.75 moles) of aluminum chloride in 390 ml. ofcarbon tetrachloride, saturated with acetylene and cooled in an icebath, is added over 20 minutes 201.9 g. (1.50 moles) of hexanoylchloride. After the addtion is complete, acetylene is bubbled into themixture as rapidly as it is absorbed and for 1 hour after absorptionbecomes slow. The mixture is poured onto 1700 g. of ice and 720 ml. ofsaturated brine. The organic phase is separated and the aqueous phase iswashed with ether. The combined organic phase and washings are washedwith satuated brine, dried (Na₂ SO₄) and evaporated. The residual oil iscombined with 10 g. of hydroquinone and distilled to yield a colorlessoil, b.p. 51°-52° C. (0.10 torr).

EXAMPLE 724 Preparation of 1-iodo-trans-1-octen-3-one

A mixture of 54.5 g. (0.364 mole) of sodium iodide and 40 g. (0.249mole) of 1-chloro-trans-1-octen 3-one (Example 723) in 360 ml. ofacetone is stirred and refluxed for 24 hours. The reaction mixture iscooled, filtered and concentrated. The residue is partitioned betweenwater and ether. The organic phase is washed with dilute sodiumbicarbonate solution, brine, dried (MgSO₄) and evaporated to an oil.This material is used directly without purification.

EXAMPLE 725 Preparation of 1-bromo-trans-1-octen-3 one

A mixture of 68.0 g. (0.424 mole) of 1-chloro-trans-1-octen-3 one(Example 723) and 444 g. (4.24 moles) of anhydrous lithium bromide in900 ml. of 2-pentanone is refluxed for 30 minutes, cooled, andpartitioned between ice water and ether. The organic phase is washedwith water and saturated brine, dried (NaSO₄), and evaporated to an oil.This material is used directly without purification.

EXAMPLE 726 Preparation of 1-bromo-trans-1-octen-3-ol

To an ice cooled mixture of 14.29 g. (0.378 mole) of sodium borohydridein 400 ml. of anhydrous ethanol is added the crude1-bromo-trans-1-octen-3-one (Example 725), from 0.424 mole of1-chloro-trans-1-octen-3-one) over 30 minutes. The mixture is stirredfor 2 hours with ice cooling and is then partitioned between ice waterand benzene. The organic phase is washed with water and saturated brine,dried (Na₂ SO₄), and evaporated to an oil. Fractional distillationyields the title compound as a colorless oil, b.p. 66°-68° C. (0.025torr).

EXAMPLE 727 Preparation of 1-chloro-trans-1-octen-3-ol

Treatment of 1-chloro-trans-1-octen-3-one (Example 723) with sodiumborohydride in the manner of Example 726 is productive of the subjectcompound.

EXAMPLE 728 Preparation of 1-bromo-3-triphenylmethoxy-trans-1-octene

A mixture of 6.212 g. (0.030 mole) of 1-bromo-trans-1-octen-3-ol(Example 726) and 10.67 g. (0.033 mole) of triphenylmethyl bromide in 40ml. of pyridine is heated to 100° C. for 1.5 hours under an inertatmosphere. The mixture is cooled and filtered. The filtrate ispartitioned between ice water and ether. The organic phase is washedwith cold dilute hydrochloric acid, saturated sodium bicarbonatesolution, and saturated brine, dried (NaSO₄), and evaporated to an oil.The latter is dissolved in hexane and passed through 250 g. of Florisil®to yield after evaporation a colorless oil. Found for C₂₇ H₂₉ OBr: C,72.13; H, 6.61; Br, 17.57.

EXAMPLE 729 Preparation of 1-iodo-trans-1-octen-3-ol

Treatment of 63 g. (0.25 mole) of 1-iodo-trans-1-octen-3-one (Example724) with sodium borohydride in the manner described in Example 726 gave58 g. of yellow oil. The oil is purified by adsorption chromatography ona magnesia silica gel column using benzene as eluent to give a lightyellow oil.

EXAMPLE 730 Preparation of 1-iodo-3-triphenylmethoxy-trans-1-octene

Treatment of 7.62 g. (0.03 mole) of 1-iodo-trans-1-octen-3-ol with 10.67g. (0.033 mole) of triphenylmethyl bromide in pyridine in the mannerdescribed in Example 728 gave 13.448 g. (90%) of a colorless oil.

EXAMPLE 731 Preparation of 1-chloro-3-triphenylmethoxy-trans-1-octene

Treatment of 1-chloro-trans-1-octen-3-ol (Example 727) withtriphenylmethyl chloride by the method described in Example 728 exceptthat the heating period is extended to six hours provides the subjectcompound.

EXAMPLE 732 Preparation of 11-deoxy-prostaglandin-E₁ methyl ester andmethyl 15-hydroxy-9-oxo-13-cis-prostenoate

To a slurry of 0.535 g. (0.022 g. atom) of magnesium in 6 ml. oftetrahydrofuran is added under an inert atmosphere 2 ml. of a solutionof 6.548 g. (0.01455 mole) of 1-bromo-3-trityloxy-trans-1-octene(Example 728) in 8 ml. of tetrahydrofuran. Reaction is initiated bywarming the mixture to 45° C. and adding 1 drop of methyl iodide. Theremainder of the halide is added at a rate to maintain a temperature of43°-46° C. and the mixture is heated at 45° C. for 1 hour after completeaddition of the halide. The Grignard reagent is cooled and added to anice cooled solution of 2.615 g. (0.0117 mole) of 2-(6-carbomethoxyhexyl)2-cyclopentenone (Example 83) and 0.229 g. of Copper (I)iodide-tri-in-butylphosphine in 6 ml. of ether over 6 minutes. Themixture is stirred with ice cooling for 30 minutes and poured into 200ml. of saturated ammonium chloride. The mixture is extracted into etherand the organic phase is washed with water and saturated brine, dried(NaSO₄) and evaporated. The residual oil is heated to 80° C. for 30minutes with 80% aqueous acetic acid under an inert atmosphere. Thismixture is cooled, evaporated to dryness, and the residue is separatedby dry column chromatography on silica gel using benzene-ethyl acetate4:1 as eluent. The title compounds are isolated as oils with Δ¹³trans/Δ¹³ cis in ratio of 10:1. Complete resolution is effected withpartition chromatography [for a description see M. J. Weiss et al,Tetrahedron, 20, 357 (1964)] on acid-washed Celite-545 usingheptane:acetonitrile (Hold Back Volume=1000 ml.);11-deoxy-prostaglandin-E₁ methyl ester is obtained in Hold Back Volume3-5 and methyl 15-hydroxy-9-oxo-13-cis-prostenoate is obtained in HoldBack Volume 6-8.

EXAMPLE 733 Preparation of 11-deoxy-prostaglandin-E₁ methyl ester andmethyl 15-hydroxy-9-oxo-13-cis-prostenoate

To a slurry of 0.243 g. (0.010 g. atom) of magnesium in 4 ml. oftetrahydrofuran is added under an inert atmosphere 2 ml. of a solutionof 4.494 g. (0.010 mole) of 1-bromo-3-trityloxy-trans-1-octene in 4 ml.of tetrahydrofuran. Reaction is initiated by warming the mixture to 65°C. and adding 1 drop of methyl iodide. The remainder of the halide isadded at a rate to maintain a temperature of 65°-70° C. and the mixtureis heated at 75°-80° C. for 30 minutes after complete addition of thehalide. The Grignard reagent is cooled and added to 2.243 g. (0.010mole) of 2-(6-carbomethoxyhexyl)-2-cyclopentenone and 0.200 g. of copper(I) iodide-tri-n-butylphosphine in 6 ml. of ether and worked up withsaturated ammonium chloride solution and aqueous acetic acid in themanner of Example 121. The products are isolated as described in Example732 to yield 11-deoxy-prostaglandin E₁ methyl ester and methyl15-hydroxy-9-oxo-13-cis-prostenoate in a ratio of 2:1.

EXAMPLE 734 Preparation of 15-hydroxy-9-oxo-13-cis-prostenoic acid

Methyl 15-hydroxy-9-oxo-13-cis-prostenoic acid is treated with potassiumhydroxide in aqueous methanol and worked up as described in Example 495to yield the title compound, m.p. 71°-75° C.

EXAMPLE 735 Preparation of Prostaglandin-E₁ and9-oxo-11α,15-dihydroxy-13-cis-prostenoic acid

A Grignard reagent is prepared as described in Example 732 from 0.535 g.(0.022 g. atom) of magnesium, 6.742 g. (0.015 mole) of1-bromo-3-triphenylmethoxy-trans-1-octene (Example 728), and 11 ml. oftetrahydrofuran at a temperature of 40°-42° C. The Grignard reagent isadded to 3.95 g. of2-(6-carbotetrahydropyranyloxyhexyl)-4-tetrahydropyranyloxy-2-cyclopentenone(Example 95) and 0.589 g. of copper (I) iodide tri-n-butylphosphine in10 ml. of tetrahydrofuran and is worked up with ammonium chloride asdescribed in Example 732. The protecting groups are removed by treatingthe worked up material, as described in Example 121, with 320 mol ofacetic acid-water-tetrahydrofuran 2:1:1 at 45° C. and the products areisolated by chromatography on silica gel with a benzene-ethyl acetategradient and resolved via partition chromatography on acid-washed Celite545.

EXAMPLE 736 Preparation of Prostaglandin-E₁, and9-oxo-11α,15-dihydroxy-13-cis-prostenoic acid

Treatment of2-(6-carbotetrahydropyranylhexyl)-4-tetrahydropyranyloxy-2-cyclopentenone(Example 95) with the Grignard reagent prepared from1-bromo-3-triphenylmethoxy-trans-1-octene (Example 728) in the presenceof Copper (I) iodide tri-n-butylphosphine complex by the proceduredescribed in Example 733 is productive of the subject compounds.

EXAMPLE 737 Preparation of 9α,15-dihydroxy-13-trans-prostenoic acid

To a solution of 433 mg. of 9-oxo-15-hydroxy-13-trans-prostenoic acid in4.5 ml. of tetrahydrofuran, stirred in an ice bath under nitrogenatmosphere, is added dropwise 3.7 ml. of 0.76 M lithiumperhydro-9b-boraphenalylhydride. After 40 minutes at 0° C. there isadded 1.62 ml. of 3 N sodium hydroxide followed by 1.62 ml. of 30%hydrogen peroxide. Ether is added and the resulting solution isacidified with 2 N hydrochloric acid. The ether layer is washed severaltimes with saturated sodium chloride solution, dried with anhydrousmagnesium sulfate and taken to dryness to give the subject product as anoil.

EXAMPLES 738-893

Treatment of the 9-oxo derivatives designated in the table below withlithium perhydro-9b-boraphenalyl hydride by the procedure described inExample 737 provides the 9α,15-dihydroxy derivatives of the table.

                  TABLE 9                                                         ______________________________________                                                Starting 9-oxo-                                                       Ex-     derivative of Product 9α,15-Dihydroxy                           ample   Example       Derivative                                              ______________________________________                                        738     375           9α,15-dihydroxy-5,6,7-                                                  trinor-13-trans-prosten-                                                      oic acid                                                739     376           9α,15-dihydroxy-7a,7b-                                                  bishomo-13-trans-pros-                                                        tenoic acid                                             740     377           9α,15-dihydroxy-2-ethyl-                                                13-trans-prostenoic                                                           acid                                                    741     378           9α,15-dihydroxy-3,3-di-                                                 methyl-13-trans-posten-                                                       oic acid                                                742     379           9α,15-dihydroxy-3-oxa-                                                  13-trans-postenoic                                                            acid                                                    743     380           9α,15-dihydroxy-7-nor-                                                  13-trans-prostenoic                                                           acid                                                    744     381           9α,15-dihydroxy-2-fluoro-                                               13-trans-prostenoic acid                                745     382           9α,15-dihydroxy-7a-homo-                                                13-trans-prostenoic acid                                746     383           9α,15-dihydroxy-2-phenyl-                                               13-trans-prostenoic acid                                747     384           9α,15-dihydroxy-2-methyl-                                               13-trans-prostenoic acid                                748     385           9α,15-dihydroxy-10a-homo-                                               13-trans-prostenoic acid                                749     386           9α,15-dihydroxy-10a-homo-                                               5,6,7-trinor-13-trans-                                                        prostenoic acid                                         750     387           9α,15-dihydroxy-10a-homo-                                               7-nor-13-trans-prosten-                                                       oic acid                                                751     388           9α,15-dihydroxy-7a,10a-                                                 bishomo-13-trans-pros-                                                        tenoic acid                                             752     389           9α,15-dihydroxy-3-thia-                                                 13-trans-prostenoic                                                           acid                                                    753     390           9α,15-dihydroxy-13-trans-                                               prostenoic acid                                         754     391           9α,15-dihydroxy-13-trans-                                               prostenoic acid                                         755     392           9α,15-dihydroxy-13-trans-                                               prostenoic acid                                         756     393           9α,15-dihydroxy-13-trans-                                               prostenoic acid                                         757     394           9α,15-dihydroxy-5-cis,13-                                               trans-prostadienoic acid                                758     395           9α,15-dihydroxy-20-nor-                                                 13-trans-prostenoic acid                                759     396           9α,15-dihydroxy-20-meth-                                                yl-13-trans-prostenoic                                                        acid                                                    760     397           9α,15-dihydroxy-16-ethyl-                                               13-trans-prostenoic acid                                761     398           9α,15-dihydroxy-16-meth-                                                yl-20-nor-13-trans-pros-                                                      tenoic acid                                             762     399           9α,15-dihydroxy-19-meth-                                                yl-13-trans, 18-prosta-                                                       dienoic acid                                            763     400           9α,15-dihydroxy-18,19-di-                                               methyl-13-trans, 18-pros-                                                     tadienoic acid                                          764     401           9α,15-dihydroxy-13-trans,                                               17-cis-prostadienoic acid                               765     402           9α,15-dihydroxy-5,6,7-                                                  trinor-13-trans, 17-cis-                                                      prostadienoic acid                                      766     403           9α,15-dihydroxy-6,7-di-                                                 nor-13-trans, 17-cis-                                                         prostadienoic acid                                      767     404           9α,15-dihydroxy-7a,7b-                                                  bishomo-13-trans, 17-                                                         cis-prostadienoic acid                                  768     405           9α,15-dihydroxy-2-ethyl-                                                13-trans, 17-cis-pros-                                                        tadienoic acid                                          769     406           9α,15-dihydroxy-3,3-di                                                  methyl-13-trans, 17-cis-                                                      prostadienoic acid                                      770     407           9α,15-dihydroxy-3-oxa-                                                  13-trans, 17-cis-pros-                                                        tadienoic acid                                          771     408           9α,15-dihydroxy-7-nor-                                                  13-trans, 17-cis-pros-                                                        tadienoic acid                                          772     409           9α,15-dihydroxy-2-fluoro-                                               13-trans, 17-cis-pros-                                                        tadienoic acid                                          773     410           9α,15-dihydroxy-7a-homo-                                                13-trans, 17-cis-pros-                                                        tadienoic acid                                          774     411           9α ,15-dihydroxy-2-phen-                                                yl-13-trans, 17-cis-                                                          prostadienoic acid                                      775     412           9α,15-dihydroxy-2-meth-                                                 yl-13-trans, 17-cis-                                                          prostadienoic acid                                      776     413           9α,15-dihydroxy-10a-ho-                                                 mo-13-trans, 17-cis-                                                          prostadienoic acid                                      777     414           9α,15-dihydroxy-10a-ho-                                                 mo-5,6,7-trinor-13-                                                           trans, 17-cis-prostadi-                                                       enoic acid                                              778     415           9α,15-dihydroxy-10a-ho-                                                 mo-7-nor-13-trans, 17-                                                        cis-prostadienoic acid                                  779     416           9α,15-dihydroxy-7a, 1Ca-                                                bishomo-13-trans, 17-                                                         cis-prostadienoic acid                                  780     417           9α,15-dihydroxy-3-thia-                                                 13-trans, 17-cis-pros-                                                        tadienoic acid                                          781     418           9α,15-dihydroxy-13-                                                     trans, 17-cis-prostadi-                                                       enoic acid                                              782     419           9α,15-dihydroxy-13-                                                     trans, 17-cis-prostadi-                                                       enoic acid                                              783     420           9α,15-dihydroxy-13-                                                     trans, 17-cis-prostadi-                                                       enoic acid                                              784     421           9α,15-dihydroxy-13-trans,                                               17-cis-prostadienoic acid                               785     422           9α,15-dihydroxy-5,6,7-                                                  trinor-19-isobutyl-13-                                                        trans, 18-prostadien-                                                         oic acid                                                786     423           9α,15-dihydroxy-5,6,7,-                                                 19,20-pentanor-13-trans,                                                      17-prostadienoic acid                                   787     424           9α,15-dihydroxy-19,20-di-                                               nor-13-trans, 18-prosta-                                                      dienoic acid                                            788     425           9α,15-dihydroxy-17,20-di-                                               methyl-20-isopropenyl-13-                                                     trans-prostanoic acid                                   789     426           9α,15-dihydroxy-16-ethyl-                                               6,7,19,20-tetranor-13-                                                        trans-prostenoic acid                                   790     427           9α,15-dihydroxy-18,19-                                                  dimethyl-6,7,-dinor-13-                                                       trans, 18-prostadienoic                                                       acid                                                    791     428           9α,15-dihydroxy-16-ethyl                                                7a,7b-bishomo-13-trans-                                                       prostenoic acid                                         792     429           9α,15-dihydroxy-19-meth-                                                yl-7a,7b-bishomo-13-                                                          trans, 18-prostadienoic                                                       acid                                                    793     430           9α,15-dihydroxy-2-ethyl-                                                19,20-dinor-13-trans-                                                         prostenoic acid                                         794     432           9α,15-dihydroxy-2-ethyl-                                                16-methyl-20-nor-13-                                                          trans-prostenoic acid                                   796     433           9α,15-dihydroxy-2-ethyl-                                                18,19-dimethyl-13-                                                            trans, 18-prostadienoic                                                       acid                                                    797     434           9α,15-dihydroxy-3,3-di-                                                 methyl-18,19,20-trinor-                                                       13-trans-prostenoic                                                           acid                                                    798     435           9α,15-dihydroxy-3,3,20-                                                 trimethyl-13-trans-                                                           prostenoic acid                                         799     436           9α,15-dihydroxy-3,3,16-                                                 trimethyl-20-nor-13-                                                          trans-postenoic acid                                    800     437           9α,15-dihydroxy-3,3-di-                                                 methyl-19-isobutyl-13-                                                        trans, 18-prostadienoic                                                       acid                                                    801     438           9α,15-dihydroxy-3,3-di-                                                 methyl-19,20-dinor-13-                                                        trans, 17-prostadienoic                                                       acid                                                    802     439           9α,15-dihydroxy-3-oxa-20-                                               nor-13-trans-prostenoic                                                       acid                                                    803     440           9α,15-dihydroxy-3-oxa-20-                                               methyl-13-trans-prosten-                                                      oic acid                                                804     441           9α,15-dihydroxy-3-oxa-16-                                               ethyl-13-trans-prosten-                                                       oic acid                                                805     442           9α,15-dihydroxy-3-oxa-16-                                               methyl-20-nor-13-trans-                                                       prostenoic acid                                         806     443           9α,15-dihydroxy-3-oxa-                                                  19,20-dinor-13-trans, 17-                                                     prostadienoic acid                                      807     444           9α,15-dihydroxy-7,19,20-                                                trinor-13-trans, 17-                                                          prostadienoic acid                                      808     445           9α,15-dihydroxy-7-nor-                                                  18,19-dimethyl-13-trans,                                                      18,prostadienoic acid                                   809     446           9α,15-dihydroxy-7,18,19,-                                               20-tetranor-16-methyl-13-                                                     trans-prostenoic acid                                   810     447           9α,15-dihydroxy-2-fluoro-                                               20-nor-13-trans-prosten-                                                      oic acid                                                811     448           9α,15-dihydroxy-2-fluoro-                                               20-ethyl-13-trans-pros-                                                       tenoic acid                                             812     449           9α,15-dihydroxy-2-fluoro-                                               16-ethyl-19,20-dinor-13-                                                      trans-prostenoic acid                                   813     450           9α,15-dihydroxy-2-fluoro-                                               16-methyl-20-nor-13-                                                          trans-prostenoic acid                                   814     451           9α,15-dihydroxy-2-fluoro-                                               19-methyl-13-trans, 18-                                                       prostadienoic acid                                      815     452           9α,15-dihydroxy-7a-homo-                                                18,19-dimethyl-13-trans,                                                      18-prostadienoic acid                                   816     453           9α,15-dihydroxy-7a-homo-                                                19,20-dinor-13-trans,                                                         17-prostadienoic acid                                   817     454           9α,15-dihydroxy-2-phenyl-                                               20-nor-13-trans-prosten-                                                      oic acid                                                818     455           9α,15-dihydroxy-2-phenyl-                                               20-ethyl-13-trans-pros-                                                       tenoic acid                                             819     456           9α,15-dihydroxy-2-phenyl-                                               16-ethyl-13-trans-pros-                                                       tenoic acid                                             820     484           9α,15-dihydroxy-20-nor-5-                                               cis, 13-trans-prostadi-                                                       enoic acid                                              821     485           9α,15-dihydroxy-20-meth-                                                yl-5-cis, 13-trans-pros-                                                      tadienoic acid                                          822     486           9α,15-dihydroxy-16-ethyl-                                               5-cis, 13-trans-prosta-                                                       dienoic acid                                            823     487           9α,15-dihydroxy-16-meth-                                                yl-20-nor-5-cis, 13-                                                          trans-prostadienoic                                                           acid                                                    824     488           9α,15-dihydroxy-19-meth-                                                yl-5-cis, 13-trans, 18-                                                       prostatrienoic acid                                     825     489           9α,15-dihydroxy-18,19-                                                  dimethyl-5-cis, 13-                                                           trans, 18-prostatrien-                                                        oic acid                                                826     490           9α,15-dihydroxy-19,20-di-                                               nor-5-cis, 13-trans, 17-                                                      prostatrienoic acid                                     827     491           9α,15-dihydroxy-5-cis,-                                                 13-trans, 17-cis-prosta-                                                      trienoic acid                                           828     734           9α,15-dihydroxy-13-cis-                                                 prostenoic acid                                         829     735           9α,11α,15-trihydroxy-13-                                          cis-protenoic acid                                      830     615           9α,15-dihydroxy-2-ethyl-                                                prostanoic acid                                         831     616           9α,15-dihydroxy-3,3-di-                                                 methyl-prostanoic acid                                  832     617           9α,15-dihydroxy-3-oxa-                                                  prostanoic acid                                         833     618           9α,15-dihydroxy-2-fluoro-                                               prostanoic acid                                         834     619           9α,15-dihydroxy-2-phenyl-                                               prostanoic acid                                         835     620           9α,15-dihydroxy-2-meth-                                                 yl-prostanoic acid                                      836     621           9α,15-dihydroxy-3-thia-                                                 prostanoic acid                                         837     622           9α,15-dihydroxy-5-cis-                                                  prostenoic acid                                         838     623           9α,15-dihydroxy-2-ethyl-                                                19,20-dinor-prostanoic                                                        acid                                                    839     624           9α,15-dihydroxy-3,3-di-                                                 methyl-19,20-dinor-pros-                                                      tanoic acid                                             840     625           9α,15-dihydroxy-3-oxa-                                                  19,20-dinor-prostanoic                                                        acid                                                    841     626           9α,15-dihydroxy-2-fluoro-                                               19,20-dinor-prostanoic                                                        acid                                                    842     627           9α,15-dihydroxy-2-phenyl-                                               19,20-dinor-prostanoic                                                        acid                                                    843     628           9α,15-dihydroxy-2-meth-                                                 yl-19,20-dinor-prostan-                                                       oic acid                                                844     629           9α,15-dihydroxy-3-thia-                                                 19,20-dinor-prostanoic                                                        acid                                                    845     630           9α,15-dihydroxy-19,20-di-                                               nor-5-cis-prostenoic acid                               846     631           9α,15-dihydroxy-16-pros-                                                tynoic acid                                             847     632           9α,15-dihydroxy-6,7-di-                                                 nor-16-prostynoic acid                                  848     633           9α,15-dihydroxy-7a,7b-                                                  bishomo-16-prostynoic                                                         acid                                                    849     634           9α,15-dihydroxy-2-ethyl-                                                16-prostynoic acid                                      850     635           9α,15-dihydroxy-3,3-di-                                                 methyl-16-prostynoic -  acid                            851     636           9α,15-dihydroxy-3-oxa-16-                                               prostynoic acid                                         852     637           9α,15-dihydroxy-7-nor-16-                                               prostynoic acid                                         853     638           9α,15-dihydroxy-2-fluoro-                                               16-prostynoic acid                                      854     639           9α,15-dihydroxy-7a-homo-                                                16-prostynoic acid                                      855     640           9α,15-dihydroxy-2-phenyl-                                               16-prostynoic acid                                      856     641           9α,15-dihydroxy-2-methyl-                                               16-prostynoic acid                                      857     642           9α,15-dihydroxy-3-thia-                                                 16-prostynoic acid                                      858     643           9α,15-dihydroxy-10a-ho-                                                 mo-16-prostynoic acid                                   859     644           9α,15-dihydroxy-10a-ho-                                                 mo-7-nor-16-prostynoic                                                        acid                                                    860     645           9α,15-dihydroxy-7a,10a-                                                 bishomo-16-prostynoic                                                         acid                                                    861     646           9α,15-dihydroxy-16-yne-                                                 5-cis-prostenoic acid                                   862     683           9α,15-dihydroxy-16-trans-                                               prostenoic acid                                         863     684           9α,15-dihydroxy-6,7-di-                                                 nor-16-trans-prostenoic                                                       acid                                                    864     685           9α,15-dihydroxy-7a,7b-                                                  bishomo-16-trans-pros-                                                        tenoic acid                                             865     686           9α,15-dihydroxy-2-ethyl-                                                16-trans-prostenoic acid                                866     687           9α,15-dihydroxy-3,3-di-                                                 methyl-16-trans-prosten-                                                      oic acid                                                867     688           9α,15-dihydroxy-3-oxa-16-                                               trans-prostenoic acid                                   868     689           9α,15-dihydroxy-7-nor-16-                                               trans-prostenoic acid                                   869     690           9α,15-dihydroxy-2-fluoro-                                               16-trans-prostenoic acid                                870     691           9α,15-dihydroxy-7a-homo-                                                16-trans-prostenoic acid                                871     692           9α,15-dihydroxy-2-phenyl-                                               16-trans-prostenoic acid                                872     693           9α,15-dihydroxy-2-methyl-                                               16-trans-prostenoic acid                                873     694           9α,15-dihydroxy-3-thia-                                                 16-trans-prostenoic acid                                874     695           9α,15-dihydroxy-10a-homo-                                               16-trans-prostenoic acid                                875     696           9α,15-dihydroxy-10a-homo-                                               7-nor-16-trans-prosten-                                                       oic acid                                                876     697           9α,15-dihydroxy-7a,10a-                                                 bishomo-16-trans-pros-                                                        tenoic acid                                             877     698           9α,15-dihydroxy-5-cis,-                                                 16-trans-prostadienoic                                                        acid                                                    878     647           9α,15-dihydroxy-16-cis-                                                 prostenoic acid                                         879     648           9α,15-dihydroxy-6,7-di-                                                 nor-16-cis-prostenoic                                                         acid                                                    880     649           9α,15-dihydroxy-7a,7b-                                                  bishomo-16-cis-prosten-                                                       oic acid                                                881     650           9α,15-dihydroxy-2-ethyl-                                                16-cis-prostenoic acid                                  882     651           9α,15-dihydroxy-3,3-di-                                                 methyl-16-cis-prosten-                                                        oic acid                                                883     652           9α,15-dihydroxy-3-oxa-                                                  16-cis-prostenoic acid                                  884     653           9α,15-dihydroxy-7-nor-                                                  16-cis-prostenoic acid                                  885     654           9α,15-dihydroxy-2-fluoro-                                               16-cis-prostenoic acid                                  886     655           9α,15-dihydroxy-7a-homo-                                                16-cis-prostenoic acid                                  887     656           9α,15-dihydroxy-2-phenyl-                                               16-cis-prostenoic acid                                  888     657           9α,15-dihydroxy-2-methyl-                                               16-cis-prostenoic acid                                  889     658           9α,15-dihydroxy-3-thia-                                                 16-cis-prostenoic acid                                  890     659           9α,15-dihydroxy-10a-ho-                                                 mo-16-cis-prostenoic                                                          acid                                                    891     660           9α,15-dihydroxy-10a-ho-                                                 mo-7-nor-16-cis-prosten-                                                      oic acid                                                892     661           9α,15-dihydroxy-7a,10a-                                                 bishomo-16-cis-prosten-                                                       oic acid                                                893     662           9α,15-dihydroxy-5-cis,-                                                 16-cis-prostadienoic                                                          acid                                                    ______________________________________                                    

EXAMPLE 894 Preparation of 2-carbalkoxy(methyl/ethyl)-2-(2-methoxyethyl)-cyclopentan-1-one

Treatment of 2-cyclopentanone carboxylate (mixed methyl and ethylesters) with 2-methoxyethyl bromide by the method of Example 1 furnishesthe subject compound as an oil, b.p. 90° C. (0.1 mm).

EXAMPLE 895 Preparation of 2-(2-methoxyethyl)cyclopentan-1-one

Heating 8 g. of 2-carboalkoxy(methyl/ethyl)2-(2-methoxyethyl)-cyclopentan-1-one (Example 894) in 8ml. of 20% aqueous hydrochloric acid at reflux for 3.5 hours andisolating the product by the method of Example 2 furnishes the subjectcompound as an oil, b.p. 45°-50° C. (0.02 mm).

EXAMPLE 896 Preparation of 1-acetoxy-2-(2-methoxyethyl)cyclopent-1-ene

The subject compound is prepared from2-(2-methoxyethyl)cyclopentan-1-one (Example 895) and acetic anhydrideby the procedure of Example 10. The product is an oil, b.p. 60° C. (0.2mm.).

EXAMPLE 897 Preparation of 2-(2-hydroxyethyl)-cyclopent-2-en-1-one

The enol acetate of Example 896 is brominated and dehydrobrominated bythe method described in Example 13. The crude product is then dissolvedin methylene chloride and is added a7-78° C. to a methylene chloridesolution containing about seven molar equivalents of boron tribromide.After one hour at -78° C. the solution is allowed to warm to roomtemperature and is then kept at ambient temperatures for a total ofeighteen hours. The mixture is poured into water and extracted withether. The organic phase is washed with saturated saline solution, thenwater and is dried. Evaporation of solvents leaves subject product,which is purified by distillation. The combined organic phases arewashed with ice cold 5% sodium hydroxide solution, ice cold 5%hydrochloric acid, and saturated sodium chloride solution, dried withanhydrous magnesium sulfate and taken to dryness. Distillation gives apale yellow oil; λmax 5.85μ (carbonyl group).

EXAMPLE 898 Preparation of 2-formylmethylcycopent-2-en-1-one

Chromium trioxide (0.6 mol) is added to a stirring solution of (1.2 mol)of anhydrous pyridine in 1500 ml. of anhydrous methylene chloride cooledin an ice bath. The deep red suspension is stirred for 15 minutes at 0°C. and 45 minutes at ambient temperature. A solution of 01.5 mol of2-(2-hydroxyethyl)-cyclopent-2-en-1-one (Example 897) in 50 ml. ofmethylene chloride is added, all at once, to the suspension. A blackterry deposit is formed immediately. After stirring the mixture for 25minutes at ambient temperature, the methylene chloride is decanted fromthe tarry precipitate which is then triturated several times with ether.

EXAMPLE 899 Preparation of2-(6-carboxy-2-cis-hexenyl)-cyclopent-2-en-1-one

A mixture of 0.194 g. (0.007952 mole) of sodium hydride (free of mineraloil) and 5.5 ml. of dimethylsulfoxide is heated to 70° C. until gasevolution ceases under a nitrogen atmosphere. The resulting solution iscooled below room temperature, and treated with a solution of 1.400 g.(0.00316 mole) of 4-carboxybutyltriphenyl phosphonium bromide [E. J.Corey et al., J. Am. Chem. Soc., 91, 5675 (1969)] in 6 ml. ofdimethylsulfoxide. To the resulting red solution is added 0.00263 moleof 2-formylmethylcyclopent-2-en-1-one (Example 898) in 2 ml. ofdimethylsulfoxide and the mixture is stirred at room temperature for2.25 hours. The mixture is poured into ice water, sodium hydroxidesolution is added to pH 12, and the neutral materials are extracted withdiethyl ether. The basic phase is acidified with dilute hydrochloricacid and in extracted with diethyl ether. The organic phase is washedwith water and saturated brine, dried (Na₂ SO₄), and evaporated to asemicrystalline mass. The latter is triturated with hot hexane, thesolids are filtered off, and the filtrate is evaporated to yield thesubject product as an oil.

EXAMPLE 900 Preparation of2-(6-carbomethoxy-2-cis-hexenyl)-cyclopent-2-en-1-one

Treatment of 2-(6-carboxy-2-cis-hexenyl)-cyclopent-2-en-1-one (Example899) with diazomethane in the usual manner is productive of the subjectester.

EXAMPLES 901-909

Hydrogenation of 13-trans-prostenoic acid designated in the table belowby the procedure of Example 899 is productive of the prostanoic acids ofthe table.

                  TABLE 10                                                        ______________________________________                                                Starting 13-                                                                  trans-pro-      Product                                               Ex-     stenoic acid    Prostanoic                                            ample   of Example      Acid                                                  ______________________________________                                        901     397             9-oxo-15-hydroxy-                                                             16-ethyl-pro-                                                                 stanoic acid                                          902     398             9-oxo-15-hydroxy-                                                             16-methyl-20-                                                                 nor-prostanoic                                                                acid                                                  903     400             9-oxo-15-hydroxy-                                                             18,19-dimethyl-                                                               prostanoic acid                                       904     426             9-oxo-15-hydroxy-                                                             16-ethyl-6,7,19,                                                              20-tetranor-pro-                                                              stanoic acid                                          905     428             9-oxo-15-hydroxy-                                                             16-ethyl-7a,7b-                                                               bishomo-prostan-                                                              oic acid                                              906     429             9-oxo-15-hydroxy-                                                             19-methyl-7a,7b-                                                              bishomo-prostan-                                                              oic acid                                              907     433             9-oxo-15-hydroxy-                                                             2-ethyl-18,19-                                                                dimethyl-pro-                                                                 stanoic acid                                          908     436             9-oxo-15-hydroxy-                                                             3,3,16-trimethyl-                                                             20-nor-prostanoic                                                             acid                                                  909     476             9-oxo-15-hydroxy-                                                             7a,10a-bishomo-16-                                                            methyl-20-nor-                                                                prostanoic acid                                       ______________________________________                                    

EXAMPLES 910-915

Treatment of the 9-oxo-alkyl esters designated in the table below withsodium borohydride by the procedure described in Example 257 isproductive of the corresponding 9-hydroxy derivative of the table. Theseproducts are obtained as 9α- and 9β-hydroxy epimeric mixtures.

                  TABLE 11                                                        ______________________________________                                                Starting 9-oxo                                                        Ex-     derivative of Product                                                 ample   Example       9α/9β-hydroxy derivative                     ______________________________________                                        910     260           ethyl 9α/9β,15-dihydroxy-                                          2-ethyl-13-trans-                                                             prostenoate                                             911     261           ethyl 9α/9β,15-dihydroxy-                                          3,3-dimethyl-13-trans-                                                        prostenoate                                             912     262           ethyl 9α/9β,15-dihydroxy-                                          3-oxa-13-trans-                                                               prostenoate                                             913     266           ethyl 9α/9β,15-dihydroxy-                                          2-phenyl-13-trans-                                                            prostenoate                                             914     272           ethyl 9α/9β,15-dihydroxy-                                          3-thia-13-trans-                                                              prostenoate                                             915     284           ethyl 9α/9β,15-dihydroxy-                                          13-trans,17-cis-                                                              prostadienoate                                          ______________________________________                                    

EXAMPLES 916-921

Saponification of the ethyl esters designated in the table below by theprocedure described in Example 122 furnishes the carboxylic acids of thetable.

                  TABLE 12                                                        ______________________________________                                                                Product 9α/9β,15-di-                       Ex-     Starting ethyl  hydroxy-13-trans-pro-                                 ample   ester of Example                                                                              stenoic acid                                          ______________________________________                                        916     910             9α/9β,15-dihydroxy-                                                2-ethyl-13-trans-                                                             prostenoic acid                                       917     911             9α/9β,15-dihydroxy-                                                3,3-dimethyl-13-                                                              trans-prostenoic                                                              acid                                                  918     912             9α/9β,15-dihydroxy-                                                3-oxa-13-trans-                                                               prostenoic acid                                       919     913             9α/9β,15-dihydroxy-                                                2-phenyl-13-trans-                                                            prostenoic acid                                       920     914             9α/9β,15-dihydroxy-                                                3-thia-13-trans-                                                              prostenoic acid                                       921     915             9α/9β,15-dihydroxy-                                                13-trans,17cis-                                                               prostadienoic acid                                    ______________________________________                                    

EXAMPLES 922-932

Treatment of the cycloalkenones of Table 13, which follows with theGrignard reagent, prepared from1-bromo-3-triphenylmethoxy-trans-1-octene and magnesium according to theprocedure of Example 733, hydrolizing the intermediate15-O-triphenylmethyl derivatives with glacial aceticacid-tetrahydrofuran-water (4:2:1) according to the procedure of Example121, and isolating the products in the manner described in Example 732is productive of the product 9-oxo-15-hydroxy-13-cis-prostenoates and9-oxo-15-hydroxy-13-trans-prostenoates of the table.

                                      TABLE 13                                    __________________________________________________________________________         Starting cyclopentenone                                                                   Product 15-hydroxy-13-cis-                                                                     Product 15-hydroxy-13-trans-                Example                                                                            Ester of Example                                                                          prostenoate ester                                                                              prostenoate ester                           __________________________________________________________________________    922  23          ethyl 9-oxo-15-hydroxy-7a,7b-                                                                  ethyl 9-oxo-15-hydroxy-7a,7b-                                bishomo-13-cis-prostenoate                                                                     bishomo-13-trans-prostenoate                923  31          ethyl 9-oxo-15-hydroxy-2-ethyl-                                                                ethyl 9-oxo-15-hydroxy-2-                                    13-cis-prostenoate                                                                             ethyl-13-trans-prostenoate                  924  41          ethyl 9-oxo-15-hydroxy-3,3-di-                                                                 ethyl 9-oxo-15-hydroxy-3,3-di-                               methyl-13-cis-prostenoate                                                                      methyl 13-trans-prostenoate                 925  46          ethyl 9-oxo-15-hydroxy-3-oxa-                                                                  ethyl 9-oxo-15-hydroxy-3-oxa-                                13-cis-prostenoate                                                                             13-trans-prostenoate                        926  53          ethyl 9-oxo-15-hydroxy-7-nor-                                                                  ethyl 9-oxo-15-hydroxy-7-nor-                                13-cis-prostenoate                                                                             13-trans-prostenoate                        927  70          ethyl 9-oxo-15-hydroxy-2-fluoro-                                                               ethyl 9-oxo-15-hydroxy-2-                                    13-cis-prostenoate                                                                             fluoro-13-trans-prostenoate                 928  84          n-decyl 9-oxo-15-hydroxy-                                                                      n-decyl 9-oxo-15-hydroxy-                                    13-cis-prostenoate                                                                             13-trans-prostenoate                        929  99          ethyl 9-oxo-15-hydroxy-2-methyl-                                                               ethyl 9-oxo-15-hydroxy-2-                                    13-cis-prostenoate                                                                             methyl-13-trans-prostenoate                 930  111         ethyl 9-oxo-15-hydroxy-10a-homo-                                                               ethyl 9-oxo-15-hydroxy-10a-                                  13-cis-prostenoate                                                                             homo-13-trans-prostenoate                   931  118         ethyl 9-oxo-15-hydroxy-3-thia-                                                                 ethyl 9-oxo-15-hydroxy-3-                                    13-cis-prostenoate                                                                             thia-13-trans-prostenoate                   932  900         methyl 9-oxo-15-hydroxy-5-                                                                     methyl 9-oxo-15-hydroxy-5-                                   cis, 13-cis-prostadienoate                                                                     cis, 13-trans-prostadienoate                __________________________________________________________________________

EXAMPLES 933-942

Saponification of the 13-cis-prostenoate alkyl esters designated inTable 14 below by the method described in Example 122 is productive ofthe 13-cis-prostenoic acids of the Table.

                                      TABLE 14                                    __________________________________________________________________________         Starting 13-cis-prostenoate                                              Example                                                                            Ester of Example                                                                           Product 13-cis-prostenoic acids                             __________________________________________________________________________    933  922          9-oxo-15-hydroxy-7a,7b-bishomo-13-                                            cis-prostenoic acid                                         934  923          9-oxo-15-hydroxy-2-ethyl-13-cis-                                              prosenoic acid                                              935  924          9-oxo-15-hydroxy-3,3-dimethyl-13-cis-                                         prostenoic acid                                             936  925          9-oxo-15-hydroxy-3-oxa-13-cis-prostenoic acid               937  926          9-oxo-15-hydroxy-7-nor-13-cis-prostenoic acid               938  927          9-oxo-15-hydroxy-2-fluoro-13-cis-prostenoic acid            939  929          9-oxo-15-hydroxy-2-methyl-13-cis-prostenoic acid            940  930          9-oxo-15-hydroxy-10a-homo-13-cis-prostenoic acid            941  931          9-oxo-15-hydroxy-3-thia-13-cis-prostenoic acid              942  932          9-oxo-15-hydroxy-5-cis, 13-cis-prostadienoic                __________________________________________________________________________                      acid                                                    

EXAMPLES 943-954

Treatment of the 9-oxo-13-cis-prostenoic acids and esters of Table 15below with lithium perhydro-9b-boraphenalyl hydride by the proceduredescribed in Example 737 furnishes the 9α,15-dihydroxy-13-cis-prostenoicacids and esters of the table.

                                      TABLE 15                                    __________________________________________________________________________         Starting 9-oxo-13-cis-                                                        prostenoic derivative                                                    Example                                                                            of Example Product 9α,15-hydroxy-13-cis-prostenoic acid and                        esters                                                        __________________________________________________________________________    943  933        9,15-dihydroxy-7a,7b-bishomo-13-cis-prostenoic acid           944  934        9,15-dihydroxy-2-ethyl-13-cis-prostenoic acid                 945  935        9,15-dihydroxy-3,3-dimethyl-13-cis-prostenoic acid            946  936        9,15-dihydroxy-3-oxa-13-cis-prostenoic acid                   947  937        9,15-dihydroxy-7-nor-13-cis-prostenoic acid                   948  938        9,15-dihydroxy-2-fluoro-13-cis-prostenoic acid                949  939        9,15-dihydroxy-2-methyl-13-cis-prostenoic acid                950  940        9,15-dihydroxy-10a-homo-13-cis-prostenoic acid                951  941        9,15-dihydroxy-3-thia-13-cis-prostenoic acid                  952  942        9,15-dihydroxy-5-cis,-13-cis-prostadienoic acid               953  932        methyl 9,15-dihydroxy-5-cis, 13-cis-prostadienoate            954  928        n-decyl 9,15-dihydroxy-13-cis-prostenoate                     __________________________________________________________________________

EXAMPLE 955 Preparation of 1-iodo-trans-1-octen-3-ol

A solution of 78.2 g. (0.310 moles) of 1-iodo-trans-1-octen-3-one(Example 724) in 150 ml. of absolute ethanol is added dropwise over 2hours to a slurry of 6.49 g. (0.172 moles) of sodium borohydride in 50ml. of absolute ethanol cooled in an ice bath. After the addition iscomplete, the mixture is stirred for 2 hours with ice cooling and isthen poured into 1 l. of water. The mixture is extracted into benzeneand the organic phase is washed with saturated brine, dried (Na₂ SO₄)and evaporated. The resulting oil is dissolved into 400 ml. of absoluteethanol and treated with 5 mole percent of p-carboxyphenylhydrazine at70° C. for 1.5 hours to remove residual ketone. The mixture is cooledand evaporated and the residue is dissolved into 400 ml. of ether and isfiltered. The filtrate is washed with dilute sodium bicarbonate solutionand saturated brine, dried (Na₂ SO₄), and evaporated to an oil. This oilis chromatographed upon 2 Kg. of Florisil® packed in hexane and theproduct is obtained upon elution with benzene Distillation of theproduct yields a colorless oil, b.p. 74°-76° C. (0.005 tor.).

EXAMPLE 956 Preparation of1-iodo-3-(p-anisyldiphenylmethoxy)-trans-1-octene

A mixture of 14.92 g. (0.0588 mole) of 1-iodo-trans-1-octen-3-ol(Example 955) and 18.2 g. (0.0588 mole) of p-anisyldiphenylmethylchloride in 165 ml. of dry pyridine is heated at 60° C. for 18 hoursunder an inert atmosphere. The mixture is cooled and the solvent isevaporated in vacuo. The residue is partitioned between ether and water,and the organic phase is washed with water and saturated brine, dried(MgSO₄), and evaporated. The residue is chromatographed upon 300 g. ofFlorisil® packed in hexane and the product is eluted with hexane and 4:1hexane-benzene the yield a colorless oil.

EXAMPLE 957 Preparation of methyl esters of dl-11-deoxyprostaglandin-E₁and dl-11-deoxy-15-epi-prostaglandin E₁

To a solution of 6.030 g. (0.01215 mole) of1-iodo-3-triphenylmethoxy-trans-1-octene (Example 730) in 8 ml. oftoluene cooled to -78° C. under an inert atmosphere is added 5.2 ml. ofa 2.34 M solution of n-butyllithium in hexane. The resulting solution isallowed to warm to -40° C. and is maintained at this temperature for 1hour. To the solution containing 3-triphenylmethoxy-trans-1-octenyllithium is then added 5.0 ml. of a 2.44M (0.0122 mole) solution of trimethylaluminum in heptane and the mixtureis allowed to warm to -10° C. The mixture containing lithiumtrimethyl(3-triphenylmethoxy-trans-1-octenyl)alanate is then cooled to-78° C. and to it is added a solution of 2.725 g. (0.01214 mole) of2-(6-carbomethoxyhexyl)-2-cyclopentenone (Example 83) dissolved in 10ml. of diethyl ether. The mixture is allowed to warm to room temperatureand is stirred at ambient temperature for 18 hours. The mixture is thenpoured onto ice and diluted hydrochloride acid and is extracted intoether. The organic phase is washed with water and saturated brine, dried(Na₂ SO₄), and evaporated to yield a colorless oil. This oil is heatedwith 100 ml. of 80% aqueous acetic acid at 80° C. for 1 hour under aninert atmosphere. The resulting mixture is cooled and evaporated invacuo to dryness with 100 ml. of xylene to yield an oil. This oil isdry-column-chromatographed upon 400 g. of silica gel using 4:1benzene-ethyl acetate as eluent to yield a total of 2.59 g. ofdl-11-deoxyprostaglandin E₁ and dl-11-deoxy-15-epiprostaglandin E₁methyl esters.

EXAMPLE 958 Preparation of4-(trimethylsiloxy)-2-(6-carbotrimethylsiloxyhexyl)cyclopent-2-en-1-one

To a solution of 5 g. of2-(6-carboxyhexyl)-4-hydroxy-cyclopent-2-en-1-one (Example 94) in 10 ml.of dry N,N-dimethylformamide is added 5.4 g. of trimethylsilyl chloridein a nitrogen atmosphere. To the resulting solution cooled in a tapwater bath is added 5.05 g. of triethylamine in 10 ml. ofN,N-dimethylformamide dropwise. The resulting mixture is stirred at 60°C. in an oil-bath for 2 hours, then at ambient temperature for 18 hours.Triethylamine hydrochloride is removed by filtration and the filtrate istaken to dryness. The residual oil is distilled to give 2.6 g. ofproduct, b.p. 156°-157° C. (0.07 mm.).

EXAMPLE 958A Preparation of4-(dimethylisopropylsiloxy)-2-(6-carbodimethylisopropylsiloxyhexyl)cyclopent-2-en-1-one

Treatment of 1 g. of 2-(6-carboxyhexyl)-4-hydroxy-cyclopent-2-en-1-onein 2 ml. of dry N,N-dimethylformamide containing 1.81 g. ofdimethylisopropylsilyl chloride [E. J. Corey, R. K. Varma, J. Amer.Chem. Soc., 93, 7320 (1971)] 1.57 g. of triethylamine in 2 ml. ofN,N-dimethylformamide in the manner described in Example 958 gives 1.45g. of product after two evaporations with toluene.

EXAMPLE 959 Preparation of4-(dimethyl-t-butylsiloxy)-2-(6-carbodimethyl-t-butylsiloxyhexyl)cyclopent-2-en-1-one

To a 0° C. solution of 2.0 gm. (8.55 mole)4-hydroxy-2-(6-carboxyhexyl)cyclopent-2-en-1-one (Example 94) and 3.65gm. (54 mole) of imidazole in 5 ml. of dimethylformamide is added aslurry consisting of 4.07 gm. (27 mole) of dimethyl-t-butyl chlorosilanein 5 ml. of dimethylformamide. The slurry is rinsed in with anadditional 1 ml. of dimethylformamide. The ice-bath is removed and thesolution is stirred at 37° C. for four hours. The solution is thenpoured into 140 ml. of water and the aqueous solution is extracted twicewith 70 ml. of isomeric hexanes. The organic layers are combined, driedwith magnesium sulfate and concentrated in vacuo to an oil. Toluene (50ml.) is added twice and evaporated in vacuo to remove unwanted lowboiling impurities.

The residue is maintained under active vacuum overnight to give 3.38 gm.(7.45 mole) of an oil, that shows no hydroxyl or carboxyl absorption inthe infrared. νmax: 1720 cm⁻¹ (unsaturated ketone and silyl ester), 840,815, 795, 780 cm⁻¹ (silyl ether and silyl ester).

EXAMPLE 960 Preparation of dl-prostaglandin E₁ and dl-epi-prostaglandinE₁

To a solution of 4.790 g. (0.0091 mole) of3-(p-anisyldiphenylmethoxy)-trans-1-iodo-1-octene (Example 956) in 5 ml.of toluene cooled to -78° C. under an inert atmosphere is added 3.9 ml.of 2.34 M n-butyllithium in hexane. The resulting solution is warmed to-40° C. and is maintained at this temperature for 1 hour. To thesolution containing 3-(p-anisyldiphenylmethoxy)-trans-1-octenyllithiumis then added 3.6 ml. of a 2.44 M solution of trimethylaluminum inheptane and the mixture is allowed to warm to 0° C. The solutioncontaining lithiumtrimethyl[3-(p-anisyldiphenylmethoxy)-trans-1-octenyl]alanate is thenadded to a solution of 3.30 g. (0.00726 mole) of2-(6-carbo-t-butyldimethylsiloxyhexyl)-4-(t-butyldimethylsiloxy)-2-cyclopentenone(Example 959) dissolved in 10 ml. of ether cooled to -45° C. under aninert atmosphere. The resulting solution is allowed to warm to roomtemperature and is stirred at ambient temperatures for 17 hours. Thesolution is then poured onto a mixture of 5 ml. of concentratedhydrochloric acid and 150 g. of ice. This mixture is stirred until theice melts and is extracted into ether. The organic phase is washed withice cold water and cold saturated brine, dried (Na₂ SO₄), and isevaporated (<37° C.) in vacuo. The resulting oil is then heated to 38°C. for 23 hours under an inert atmosphere with 100 ml. of 3:1:1 (V:V:V)acetic acid-tetrahydrofuran-water. The mixture is then evaporated with150 ml. of xylene in vacuo (<38° C.) to yield an oil. Chromatography ofthis oil upon 115 g. of Silic AR CC-4 (Mallinokrodt) using abenzene-ethyl acetate gradient as eluent yields dl-prostaglandin E₁,m.p. 108-112 (from ethyl acetate) and dl-15-epi-prostaglandin E₁.

EXAMPLE 961 Preparation of 3-triphenylmethoxy-trans-1-octenyllithium

To a solution of 4.96 g. of 1-iodo-3-triphenylmethoxy-trans-1-octene(Example 730) in 10 ml. of toluene cooled to -78° C. is added under aninert atmosphere 1 molar equivalent of n-butyllithium dissolved inhexane. The reaction mixture is allowed to warm to -40° C. and is thenmaintained at that temperature for 1 hour to yield a hydrocarbonsolution of 3-triphenylmethoxy-trans-1-octenyllithium.

EXAMPLE 962 Preparation of3-(p-anisyldiphenylmethoxy)-trans-1-octenyllithium

To a solution of 5.26 g. of1-iodo-3-(p-anisyldiphenylmethoxy)-trans-1-octene (Example 956) in 10ml. of toluene, cooled to -78° C., is added under an inert atmosphere 1molar equivalent of n-butyllithium dissolved in hexane. The reactionmixture is allowed to warm to -40° C. and is maintained at thattemperature for 1 hour to yield a hydrocarbon solution of3-(p-anisyldiphenylmethoxy)-trans-1-octenyllithium.

EXAMPLE 963 Preparation of lithium[3-triphenylmethoxy-trans-1-octenyl]-trimethylalanate

To a hydrocarbon solution of 3-triphenylmethoxy-trans-1-octenyllithium(Example 961) cooled to -40° C. is added under an inert atmosphere 1molar equivalent of trimethylaluminum dissolved in heptane to yield ahydrocarbon solution of the title compound.

EXAMPLE 964 Preparation of lithium[3-p-anisyldiphenylmethoxy)-trans-1-octenyl]-trimethylalanate

To a hydrocarbon solution of3-(p-anisyldiphenylmethoxy)-trans-1-octenyllithium (Example 962) cooledto -40° C. is added under an inert atmosphere 1 molar equivalent oftrimethylaluminum dissolved in hexane to yield a hydrocarbon solution ofthe title compound.

EXAMPLE 965 Preparation of lithium[3-triphenylmethoxy-trans-1-octenyl]-tri-n-propylalanate

To a hydrocarbon solution of 3-triphenylmethoxy-trans-1-octenyllithium(Example 961) cooled to -40° C. is added under an inert atmosphere 1molar equivalent of tri-n-propylaluminum dissolved in hexane to yield ahydrocarbon solution of the title compound.

EXAMPLE 966 Preparation of lithium[3-(p-anisyldiphenylmethoxy)-trans-1-octenyl]-tri-n-hexylalanate

To a hydrocarbon solution of3-(p-anisyldiphenylmethoxy)-trans-1-octenyllithium (Example 962) cooledto -40° C. is added under an inert atmosphere 1 molar equivalent totri-n-hexylaluminum dissolved in heptane to yield a hydrocarbon solutionof the title compound.

EXAMPLE 967 Preparation of lithium[3-triphenylmethoxy-trans-1-octenyl]-tri-n-decylalanate

To a hydrocarbon solution of 3-triphenylmethoxy-trans-1-octenyllithium(Example 961) cooled to -40° C. is added under an inert atmosphere 1molar equivalent of tri-n-decylaluminum dissolved in heptane to yield ahydrocarbon solution of the title compound.

EXAMPLE 968 Preparation of lithiumdi-(3-triphenylmethoxy-trans-1-octenyl)-dimethylalanate

To a hydrocarbon solution of dimethylaluminum chloride cooled to -78° C.is added under an inert atmosphere 2 molar equivalents of3-triphenylmethoxy-trans-1-octenyllithium (Example 961) dissolved intoluene-hexane solvent. The mixture is allowed to warm to 0° C. to yielda hydrocarbon solution of the title compound.

EXAMPLE 969 Preparation of lithiumdi-[3-(p-anisyldiphenylmethoxy)-trans-1-octenyl]-diethylalanate

To a hexane solution of diethylaluminum chloride cooled to -78° C. isadded under an inert atmosphere 2 molar equivalent of3-(p-anisyldiphenylmethoxy)-trans-1-octenyllithium (Example 962)dissolved in toluene-hexane solvent. The mixture is allowed to warm to0° C. to yield a hydrocarbon solution of the title compound.

EXAMPLE 970 Preparation of lithiumtri-(3-triphenylmethoxy-trans-1-octenyl)-ethylalanate

To a hydrocarbon solution of ethylaluminum dichloride cooled to -78° C.is added under an inert atmosphere 3 molar equivalents of3-triphenylmethoxy-trans-1-octenyllithium (Example 961) dissolved intoluene-hexane solvent. The mixture is allowed to warm to 0° C. to yielda hydrocarbon solution of the title compound.

EXAMPLE 971 Preparation of lithiumtetra-(3-triphenylmethoxy-trans-1-octenyl)alanate

Tp a well stirred mixture of anhydrous aluminum chloride and hexanecooled to -70° C. is added under an inert atmosphere 4 molar equivalentsof 3-triphenylmethoxy-trans-1-octenyllithium (Example 961) dissolved intoluene-hexane The mixture is allowed to warm to 0° C. to yield thetitle compound.

EXAMPLE 972 Preparation of lithiumtetra-(3-p-anisyldiphenylmethoxy-trans-1-octenyl)alanate

To a well stirred mixture of anhydrous aluminum chloride and hexanecooled to -78° C. is added under an inert atmosphere 4 molar equivalentsof 3-p-anisyldiphenylmethoxy-trans-1-octenyllithium (Example 962)dissolved in toluene-hexane. The mixture is allowed to warm to 0° C. toyield the title compound.

EXAMPLES 973-981

Substitution of lithiumtrimethyl(3-triphenylmethoxy-trans-1-octenyl)alanate in Example 957 withthe lithium alanates of Examples 964, 965, 966, 967, 968, 969, 970, 971or 972 is productive of the methyl esters of d,1-11-deoxy-prostaglandinE₁ and d,11-deoxy-15-epi-prostaglandin E₁.

EXAMPLES 982-990

Substitution of lithium trimethyl[3-(p-anisyldiphenylmethoxy)-trans-1-octenyl]alanate of Example 960 withthe lithium alanates of Examples 965, 966, 967, 968, 969, 970, 971 or972 is productive of d,1-prostaglandin-E₁ and d,1-15-epi-prostaglandinE₁.

EXAMPLE 991 Preparation of hexanoyl bromide

A mixture of 300 g. of hexanoic acid and 260 g. of phosphorus tribromideis heated at 80° C. for 1.5 hours with stirring and protection frommoisture. The mixture is cooled and the upper phase is decanted into adistilling flask. Distillation of this material yields 400 g. of thecolorless acid bromide, b.p. 51°-53° C. (10 torr.).

EXAMPLE 992 Preparation of 1-bromo-trans-1-octen-3-one

A mixture of 300 g. of aluminum bromide and 250 ml. of1,2-dibromoethane, cooled in an ice bath and protected from moisture, issaturated with acetylene. To the mixture is added with ice cooling 150g. of hexanoyl bromide (Example 991) over a period of 20 minutes and theresulting mixture is treated with acetylene until gas uptake ceases. Thereaction mixture is poured onto 500 ml. of saturated brine and 500 g. ofice. The resulting mixture is extracted twice with 500 ml. of ether. Thecombined organic extracts are washed twice with 500 ml. of saturatedbrine and dried with anhydrous sodium sulfate. To the organic phase isadded 5 g. of hydroquinone and the solvent is evaporated in vacuo toyield the crude 1-bromo-trans-1-octen-3-one.

EXAMPLE 993 Preparation of 1-bromo-trans-1-octen-3-ol

To an ice cooled mixture of 20 g. of sodium borohydride in 800 ml. ofanhydrous ethanol is added 160 g. of crude 1-bromo-trans-1-octen-3-one(Example 992) over a period of 0.5 hour. The mixture is stirred for 2hours with ice cooling and is then partitioned between ice water andbenzene. The organic phase is washed with water and saturated brine,dried (Na₂ SO₄), and evaporated to an oil. Distillation gives theproduct as an oil, b.p. 66°-68° C. (0.025 torr.).

EXAMPLE 994 Preparation of 4,4-dimethyl-1-octyn-3-ol

To a solution of 20.2 g. (0.220 mole) of lithiumacetylide-ethylenediamine complex in 100 ml. of dry dimethylsulfoxide isadded 25.6 g. (0.200 mole) of 2,2-dimethyl-1-hexanal, prepared accordingto the procedure of G. Stork and S. R. Dowd, J. Amer. Chem. Soc., 85,2178 (1963), in 25 ml. of dimethylsulfoxide at a rate to maintain atemperature of 25° C. (cooling). The mixture is then maintained at 25°C. for 2 hours and is poured onto ice and excess hydrochloric acid. Themixture is extracted with ether and the organic phase is washed withwater and saturated brine, dried (Na₂ SO₄), and evaporated to an oil.Distillation in vacuo yields the product as a colorless oil.

EXAMPLE 995 Preparation of 4,4-dimethyl-3-tetrahydropyranyloxy-1-octyne

To a solution of 23.1 g. (0.150 mole) of 4,4-dimethyl-1-octyn-3-ol(Example 994) in 126 g. of freshly distilled dihydropyran is added 1drop of phosphorus oxychloride and the solution is maintained at ambienttemperature in a tightly stoppered flask for 20 hours. Five drops oftriethylamine are then added and the mixture is evaporated in vacuo toan oil. The oil is chromatographed on 600 g. of silica gel and theproduct is eluted with 5% ethyl acetate in benzene yielding a colorlessoil.

EXAMPLE 996 Preparation of 4,4-dimethyl-1-iodo-trans-1-octen-3-ol

To 233 ml. of a 0.43 M solution of disiamylborane in diglyme cooled to0° C. under an inert atmosphere is added 23.8 g. (0.100 mole)4,4-dimethyl-3-tetrahydropyranyloxy-1-octyne (Example 995). The mixtureis allowed to come to room temperature and is stirred at ambienttemperature for 3 hours. The solution is cooled to 0° C. and 22.5 g.(0.30 mole) of triethylamine oxide is added portionwise such that thetemperature is maintained at 0°-5° C. The mixture is stirred at 0° C.for 1 hour and is then poured into 150 ml. of 1 N sodium hydroxidefollowed immediately by a solution of 25:4 g. (0.100 mole) of iodine in60 ml. of tetrahydrofuran. The mixture is stirred at ambienttemperatures for 0.5 hour and poured into 500 ml. of water. The mixtureis decolorized by addition of sodium thiosulfate solution and isextracted into ether. The organic phase is washed with water and thesolvent is removed in vacuo. The residue is stirred at room temperaturefor 20 hours with 900 ml. 3:1:1 tetrahydrofuran-acetic acid-water. Thesolution is evaporated in vacuo and the residue is chromatographed onsilica gel in benzene using 10-20% ethylacetate in benzene.

EXAMPLE 997 Preparation of4,4-dimethyl-1-iodo-3-triphenylmethoxy-trans-1-octene

Treatment of 11.2 g. (0.0396 mole) of4,4-dimethyl-1-iodo-trans-1-octen-3-ol (Example 996) with 12.8 g. oftriphenylmethyl bromide in 50 ml. of pyridine and purification onFlorisil®, all as described in Example 728 gives the title compound.

EXAMPLE 998 Preparation of 5,5-dimethyl-1-octyn 3-ol

Treatment of 20.2 g (0.220 mole) of lithium acetylide-ethylenediaminecomplex in 100 ml. of dimethylsulfoxide with 25.6 g. (0.200 mole) of3,3-dimethylhexanal [prepared according to the procedure of A. W.Burgstahler, J. Amer. Chem. Soc., 82, 4681 (1960)] and distillation ofthe product, all as described in Example 994 yields the title compound.

EXAMPLE 999 Preparation of 5,5-dimethyl-3-tetrahydropyranyloxy-1-octyne

Treatment of 23.1 g. (0.150 mole) of 5,5-dimethyl-1-octyn-3-ol (Example998) with 126 g. of dihydropyran and 1 drop of phosphorous oxychlorideas described in Example 995 gives the title compound.

EXAMPLE 1000 Preparation of 5,5-dimethyl-1-iodo-trans-1-octen-3-ol

Treatment of 23.8 g. (0.100 mole) of5,5-dimethyl-3-tetrahydropyranyloxy-1-octyne (Example 999) successivelywith 233 ml. of 0.43 M disiamylborane in diglyme, 22.5 g. oftrimethylamine oxide, 150 ml. of 1 N sodium hydroxide, 25.4 g. ofiodine, and 900 ml. of 3:3:1 tetrahydrofuran-acetic acid-water asdescribed in Example 996 gives the title compound.

EXAMPLE 1001 Preparation of5,5-dimethyl-1-iodo-3-triphenylmethoxy-trans-1-octene

Treatment of 6.0 g. of 5,5-dimethyl-1-iodo-trans-1-octen-3-ol (Example1000) with 6.9 g. of triphenylmethyl bromide in 30 ml. of pyridine andpurification on Florisil®, all as described in Example 728 gives thetitle compound.

EXAMPLE 1002 Preparation of4,4-dimethyl-3-triphenylmethoxy-trans-1-octenyllithium

Treatment of 4,4-dimethyl-1-iodo-3-triphenylmethoxy-trans-1-octene(Example 997) with n-butyllithium in the manner of Example 961 providesa toluene-hexane solution of the subject trans-vinyl lithium derivative.

EXAMPLE 1003 Preparation of5,5-dimethyl-3-triphenylmethoxy-trans-1-octenyllithium

Treatment of 5,5-dimethyl-1-iodo-3-triphenylmethoxy-trans-1-octene(Example 1001) with n-butyllithium in the manner of Example 961 providesa toluene-hexane solution of the subject trans-vinyl lithium derivative.

EXAMPLE 1004 Preparation of lithium(4,4-dimethyl-3-triphenylmethoxy-trans-1-octenyl)-trimethylalanate

The subject alanate in hydrocarbon solution is prepared according to themethod of Example 963 from a hydrocarbon solution of4,4-dimethyl-3-triphenylmethoxy-trans-1-octenyllithium (Example 1002)and trimethylaluminum.

EXAMPLE 1005 Preparation of lithium(5,5-dimethyl-3-triphenylmethoxy-trans-1-octenyl)-trimethylalanate

A hydrocarbon solution of the subject alanate is prepared from ahydrocarbon solution of 5,5-dimethyl-3-triphenylmethoxy-trans-1-octenyllithium (Example 1003) and trimethylaluminum according to the procedureof Example 963.

EXAMPLES 1006-1031

Treatment of the cycloalkenones of Table 16 which follows with theindicated alanates according to the procedure of Example 957 providesthe product 16,16-dimethyl or 17,17-dimethyl 13-trans-prostenoates ofthe table. The intermediate corresponding 15-O-triphenylmethylderivatives are obtained prior to treatment with aqueous acetic acid.

                  TABLE 16                                                        ______________________________________                                                              Product from reaction with                                                    lithium (4,4-Dimethyl-3-                                        Starting cyclo-                                                                             triphenylmethoxy-trans-1-                               Exam-   alkenone of   octenyl)trimethylalanate                                ple     Example       (Example 1004)                                          ______________________________________                                        1006    13            ethyl 9-oxo-15-hydroxy-16,-                                                   16-dimethyl-13-trans-pro-                                                     stenoate                                                1007    23            ethyl 9-oxo-15-hydroxy-16,-                                                   16-dimethyl-7a,7b-bishomo-                                                    13-trans-prostenoate                                    1008    31            ethyl 9-oxo-15-hydroxy-16,-                                                   16-dimethyl-2-ethyl-13-                                                       trans-prostenoate                                       1009    41            ethyl 9-oxo-15-hydroxy-16,-                                                   16-dimethyl-3,3-dimethyl-                                                     13-trans-prostenoate                                    1010    46            ethyl 9-oxo-15-hydroxy-16,-                                                   16-dimethyl-3-oxa-13-trans-                                                   prostenoate                                             1011    53            ethyl 9-oxo-15-hydroxy-16,-                                                   16-dimethyl-7-nor-13-trans-                                                   prostenoate                                             1012    70            ethyl 9-oxo-15-hydroxy-16,-                                                   16-dimethyl-2-fluoro-13-                                                      trans-prostenoate                                       1013    84            n-decyl 9-oxo-15-hydroxy-                                                     16,16-dimethyl-13-trans                                                       prostenoate                                             1014    99            ethyl 9-oxo-15-hydroxy-16,-                                                   16-dimethyl-2-methyl-13-                                                      trans-prostenoate                                       1015    111           ethyl 9-oxo-15-hydroxy-16,-                                                   16-dimethyl-10a-homo-13-                                                      trans-prostenoate                                       1016    118           ethyl 9-oxo-15-hydroxy-16,-                                                   16-dimethyl-3-thia-13-trans-                                                  prostenoate                                             1017    900           methyl 9-oxo-15-hydroxy-16,-                                                  16-dimethyl-5-cis,13-trans-                                                   prostadienoate                                          1018    79            ethyl 9-oxo-15-hydroxy-16,-                                                   16-dimethyl-2-phenyl-13-                                                      trans-prostenoate                                       1019    13            ethyl 9-oxo-15-hydroxy-17,-                                                   17-dimethyl-13-trans-pro-                                                     stenoate                                                1020    23            ethyl 9-oxo-15-hydroxy-17,-                                                   17-dimethyl-7a,7b-bishomo-                                                    13-trans-prostenoate                                    1021    31            ethyl 9-oxo-15-hydroxy-17,-                                                   17-dimethyl-2-ethyl-13-                                                       trans-prostenoate                                       1022    41            ethyl 9-oxo-15-hydroxy-17,-                                                   17-dimethyl-3,3-dimethyl-                                                     13-trans-prostenoate                                    1023    46            ethyl 9-oxo-15-hydroxy-17,-                                                   17-dimethyl-3-oxa-13-trans-                                                   prostenoate                                             1024    53            ethyl 9-oxo-15-hydroxy-17,-                                                   17-dimethyl-7-nor-13-trans-                                                   prostenoate                                             1025    70            ethyl 9-oxo-15-hydroxy-17,-                                                   17-dimethyl-2-fluoro-13-                                                      trans-prostenoate                                       1026    84            n-decyl 9-oxo-15-hydroxy-                                                     17,17-dimethyl-13-trans-                                                      prostenoate                                             1027    99            ethyl 9-oxo-15-hydroxy-17,-                                                   17-dimethyl-2-methyl-13-                                                      trans-prostenoate                                       1028    111           ethyl 9-oxo-15-hydroxy-17,-                                                   17-dimethyl-10a-homo-13-                                                      trans-prostenoate                                       1029    118           ethyl 9-oxo-15-hydroxy-17,-                                                   17-dimethyl-3-thia-13-trans-                                                  prostenoate                                             1030    900           methyl 9-oxo-15-hydroxy-                                                      17,17-dimethyl- 5-cis,13-                                                     trans-prostadienoate                                    1031    79            ethyl 9-oxo-15-hydroxy-17,-                                                   17-dimethyl-2-phenyl-13-                                                      trans-prostenoate                                       ______________________________________                                    

EXAMPLES 1032-1055

Saponification of the 16,16-dimethyl or 17,17-dimethyl13-trans-prostenoate alkyl esters of Table 17 below by the method ofExample 122 provides the corresponding prostenoic acids of the Table.

                  TABLE 17                                                        ______________________________________                                                              Product 16,16-dimethyl or                                       Starting alkyl                                                                              17,17-dimethyl-9-oxo-15-                                Exam-   ester of      hydroxy-13-trans-proste-                                ple     Example       noic acid                                               ______________________________________                                        1032    1006          9-oxo-15-hydroxy-16,16-di-                                                    methyl-13-trans-prostenoic                                                    acid                                                    1033    1007          9-oxo-15-hydroxy-16,16-di-                                                    methyl-7a,7b-bishomo-13-                                                      trans-prostenoic acid                                   1034    1008          9-oxo-15-hydroxy-16,16-di-                                                    methyl-2-ethyl-13-trans-                                                      prostenoic acid                                         1035    1009          9-oxo-15-hydroxy-16,16-di-                                                    methyl-3,3-dimethyl-13-                                                       trans-prostenoic acid                                   1036    1010          9-oxo-15-hydroxy-16,16-di-                                                    methyl-3-oxa-13-trans-pro-                                                    stenoic acid                                            1037    1011          9-oxo-15-hydroxy-16,16-di-                                                    methyl-7-nor-13-trans-pro-                                                    stenoic acid                                            1038    1012          9-oxo-15-hydroxy-16,16-di-                                                    methyl-2-fluoro-13-trans-                                                     prostenoic acid                                         1039    1014          9-oxo-15-hydroxy-16,16-di-                                                    methyl-2-methyl-13-trans-                                                     prostenoic acid                                         1040    1015          9-oxo-15-hydroxy-16,16-di-                                                    methyl-10a-homo-13-trans-                                                     prostenoic acid                                         1041    1016          9-oxo-15-hydroxy-16,16-di-                                                    methyl-3-thia-13-trans-                                                       prostenoic acid                                         1042    1017          9-oxo-15-hydroxy-16,16-di-                                                    methyl- 5-cis,13-trans-pro-                                                   stadienoic acid                                         1043    1018          9-oxo-15-hydroxy-16,16-di-                                                    methyl-2-phenyl-13-trans-                                                     prostenoic acid                                         1044    1019          9-oxo-15-hydroxy-17,17-di-                                                    methyl-13-trans-prostenoic                                                    acid                                                    1045    1020          9-oxo-15-hydroxy-17,17-di-                                                    methyl-7a,7b-bishomo-13-                                                      trans-prostenoic acid                                   1046    1021          9-oxo-15-hydroxy-17,17-di-                                                    methyl-2-ethyl-13-trans-                                                      prostenoic acid                                         1047    1022          9-oxo-15-hydroxy-17,17-di-                                                    methyl-3,3-dimethyl-13-                                                       trans-prostenoic acid                                   1048    1023          9-oxo-15-hydroxy-17,17-di-                                                    methyl-3-oxa-13-trans-pro-                                                    stenoic acid                                            1049    1024          9-oxo-15-hydroxy-17,17-di-                                                    methyl-7-nor-13-trans-pro-                                                    stenoic acid                                            1050    1025          9-oxo-15-hydroxy-17,17-di-                                                    methyl-2-fluoro-13-trans-                                                     prostenoic acid                                         1051    1027          9-oxo-15-hydroxy-17,17-di-                                                    methyl-2-methyl-13-trans-                                                     prostenoic acid                                         1052    1028          9-oxo-15-hydroxy-17,17-di-                                                    methyl-10a-homo-13-trans-                                                     prostenoic acid                                         1053    1029          9-oxo-15-hydroxy-17,17-di-                                                    methyl-3-thia-13-trans-pro-                                                   stenoic acid                                            1054    1030          9-oxo-15-hydroxy-17,17-di-                                                    methyl- 5-cis,13-trans-pro-                                                   stadienoic acid                                         1055    1031          9-oxo-15-hydroxy-17,17-di-                                                    methyl-2-phenyl-13-trans                                                      prostenoic acid                                         ______________________________________                                    

EXAMPLES 1056-1081

Treatment of the 9-oxo-acids and esters of Table 18 below with lithiumperhydro-9b-boraphenalyl hydride by the procedure of Example 737provides the 9α,15-dihydroxy-16,16-dimethyl or17,17-dimethyl-13-trans-prostenoic acid of the Table.

                  TABLE 18                                                        ______________________________________                                                             Product 9α-15-Dihydroxy-16,-                               Starting 9-oxo                                                                             16-dimethyl or 17,17-di-                                 Exam-   derivative of                                                                              methyl-13-trans-prostenoic                               ple     Example      acids or esters                                          ______________________________________                                        1056    1032         9α,15-dihydroxy-16,16-di-                                               methyl-13-trans-prostenoic                                                    acid                                                     1057    1033         9α,15-dihydroxy-16,16-di-                                               methyl-7a,7b-bishomo-13-                                                      trans-prostenoic acid                                    1058    1034         9α,15-dihydroxy-16,16-di-                                               methyl-2-ethyl-13-trans-                                                      prostenoic acid                                          1059    1035         9α,15-dihydroxy-16,16-di-                                               methyl-3,3-dimethyl-13-                                                       trans-prostenoic acid                                    1060    1036         9α,15-dihydroxy-16,16-di-                                               methyl-3-oxa-13-trans-pro-                                                    stenoic acid                                             1061    1037         9α,15-dihydroxy-16,16-di-                                               methyl-7-nor-13-trans-pro-                                                    stenoic acid                                             1062    1038         9α,15-dihydroxy-16,16-di-                                               methyl-2-fluoro-13-trans-                                                     prostenoic acid                                          1063    1013         n-decyl 9α,15-dihydroxy-16,-                                            16-dimethyl-13-trans-proste-                                                  noate                                                    1064    1039         9α,15-dihydroxy-16,16-di-                                               methyl-2-methyl-13-trans-                                                     prostenoic acid                                          1065    1040         9α,15-dihydroxy-16,16-di-                                               methyl-10a-homo-13-trans-                                                     prostenoic acid                                          1066    1041         9α,15-dihydroxy-16,16-di-                                               methyl-3-thia-13-trans-pro-                                                   stenoic acid                                             1067    1042         9α,15-dihydroxy-16,16-di-                                               methyl- 5-cis,13-trans-                                                       prostadienoic acid                                       1068    1043         9α,15-dihydroxy-16,16-di-                                               methyl-2-phenyl-13-trans-                                                     prostenoic acid                                          1069    1044         9α,15-dihydroxy-17,17-di-                                               methyl-13-trans-prostenoic                                                    acid                                                     1070    1045         9α,15-dihydroxy-17,17-di-                                               methyl-7a,7b-bishomo-13-                                                      trans-prostenoic acid                                    1071    1046         9α,15-dihydroxy-17,17-di-                                               methyl-2-ethyl-13-trans-                                                      prostenoic acid                                          1072    1047         9α,15-dihydroxy-17,17-di-                                               methyl-3,3-dimethyl-13-                                                       trans-prostenoic acid                                    1073    1048         9α,15-dihydroxy-17,17-di-                                               methyl-3-oxa-13-trans-pro-                                                    stenoic acid                                             1074    1049         9α,15-dihydroxy-17,17-di-                                               methyl-7-nor-13-trans-pro-                                                    stenoic acid                                             1075    1050         9α,15-dihydroxy-17,17-di-                                               methyl-2-fluoro-13-trans-                                                     prostenoic acid                                          1076    1026         n-decyl 9α,15-dihydroxy-                                                17,17-dimethyl-13-trans-                                                      prostenoate                                              1077    1051         9α,15-dihydroxy-17,17-di-                                               methyl-2-methyl-13-trans-                                                     prostenoic acid                                          1078    1052         9α,15-dihydroxy-17,17-di-                                               methyl-10a-homo-13-trans-                                                     prostenoic acid                                          1079    1053         9α,15-dihydroxy-17,17-di-                                               methyl-3-thia-13-trans-                                                       prostenoic acid                                          1080    1054         9α,15-dihydroxy-17,17-di-                                               methyl 5-cis,13-trans-pro-                                                    stadienoic acid                                          1081    1055         9α,15-dihydroxy-17,17-di-                                               methyl-2-phenyl-13-trans-                                                     prostenoic acid                                          ______________________________________                                    

EXAMPLE 1082

A solution of methyl9-oxo-15-hydroxy-5-cis,13-trans,17-cis-prostatrienoate (Example 374) intetrahydrofuran is added to 1.1 equivalent of lithiumperhydro-9b-boraphenyalyl hydride in tetrahydrofuran at -78° C. After 30minutes equal volumes of 5% aqueous sodium carbonate and 30% aqueoushydrogen peroxide is added, and the solution is stirred 15 minutes. Thesolution is diluted with water and extracted with ether. The organicphase is dried (magnesium sulfate) and concentrated in vacuo to givemethyl 9α,15α-dihydroxy-5-cis,13-trans,17-cis-prostatrienoate,contaminated with methyl9β,15α-dihydroxy-5cis,13trans,17cis-prostatienoate. The crude mixture ofesters is dissolved in methylene chloride and added to a refluxingsolution of 1.2 equivalents of 2,3-dichloro-5,6-dicyanobenzoquinone(DDQ) in methylene chloride. After 5 hours, the solution is cooled andfiltered. The filtrate is diluted with two volumes of ether, extractedwith 5% aqueous sodium carbonate and dried with magnesium sulfate. Thesolution is concentrated in vacuo to give methyl 9α-hydroxy-15-oxo-5cis-13-trans, 17cis-prostatrienoate and9β-hydroxy-15-oxo-5cis, 13trans,17cis-prostatrienoate. The crudematerial is dissolved in benzene and 1.2 equivalents each oftriethylamine and trimethylsilyl chloride is added. The triethylaminehydrochloride is removed by filtration and the solution is concentratedin vacuo to give methyl9α-trimethylsiloxy-15-keto-5cis,13trans,17cis-prostatrienoate and thecorresponding 9β-trimethylsiloxy derivative.

The siloxy derivatives are dissolved in ether at 0° C. and 1.05equivalents of methyl magnesium bromide in ether is added. After thereaction is complete, the solution is poured into saturated aqueousammonium chloride and extracted with ether. The ether is dried andconcentrated in vacuo to give methyl9α-trimethylsiloxy-15α-hydroxy-15β-methyl-5cis,13trans,17cis-prostatrienoate,and methyl9α-trimethylsiloxy-15β-hydroxy-15α-methyl-5cis,13trans,17cis-prostatrienoate,methyl9β-trimethylsiloxy-15α-hydroxy-15β-methyl-5cis,13trans,17cis-prostatrienoate,and methyl 9β-trimethylsiloxy-15β-hydroxy-15α-methyl5cis,13trans,17-'cis-prostatrienoate. Hydrolysis of the siloxy functionsof each in a solution of methanol, water and acetic acid (approximately10:1:1, 3 hours ambient temperatures) and gives methyl9α,15α-dihydroxy-15β-methyl-5cis-13trans,17-cis-prostatrienoate, methyl9α,15β-dihydroxy-15α-methyl-5cis,13trans,17cis-prostatrienoate, methyl9β,15α-dihydroxy-15β-methyl-5cis,13trans,17cis-prostatrienoate andmethyl 9β,15β-dihydroxy-15α-methyl-5-cis,13trans,17cis-prostatrienoateseparated by dry column chromatography and further purified by partitionchromatography saponification (method of Example 122) of each componentin 50% aqueous methanol with potassium hydroxide gives the correspondingfree acids.

Treatment of a solution of methyl9α,15α-dihydroxy-15β-methyl-5cis,13trans,17cis-prostatrienoate inmethylene chloride with Collins reagent (CrO₃ -pyridine in methylenechloride) gives methyl9-oxo-15α-hydroxy-15β-methyl-5cis,13trans,17cis-prostatrienoate,saponification of which (method of Example 122) gives9-oxo-15α-hydroxy-15β-methyl-5cis,13trans,17cis-prostatrienoate acid.

Similar treatment of the 15β-hydroxy esters gives methyl9-oxo-15β-hydroxy-15α-methyl-5cis,13trans,17cis-prostatrienoate whichgives 9-oxo-15β-hydroxy-15α-methyl-5cis,13trans,17cis-prostatrienoicacid after saponification.

EXAMPLES 1083-1101

Treatment of the 9-oxo-15-hydroxy prostenoic esters of Table 18A belowby the sequence of reactions described in Example 1082 is productive ofthe 9α,15-dihydroxy-15-methyl and the 9-oxo-15-hydroxy-15-methylproducts of the table. Also prepared in the course of these reactionsequences are the ethyl (methyl for Example 1101) esters correspondingto the products of the table, the 9β-hydroxy derivatives correspondingto the listed 9α-hydroxy derivatives and their ethyl esters, the 15-ketoderivatives of the 9α- and 9β-hydroxy compounds corresponding to the9-oxo starting compounds, and the 9α- or 9β-trimethylsilyloxy ethylesters of the 15-keto and 15-hydroxy-15-methyl compounds. In all casesboth the 15α-hydroxy-15β-methyl and the 15β-hydroxy-15α-methyl productsand intermediates are obtained. These epimers are separable bychromatographic procedures.

                  TABLE 18A                                                       ______________________________________                                                Starting 9-oxo-                                                       Ex-     15-hydroxy-ester                                                                             Product 15-hydroxy-                                    ample   of Example     15-methyl derivative                                   ______________________________________                                        1083    260            9-oxo-15-methyl-15-                                                           hydroxy-2-ethyl-13-                                                           trans-prostenoic acid                                                         and 9α,15-dihydroxy-                                                    15-methyl-2-ethyl-13-                                                         trans-prostenoic acid                                  1084    261            9-oxo-15-hydroxy-15-                                                          methyl-3,3-dimethyl-                                                          13-trans-prostenoic                                                           acid and 9α,15-di-                                                      hydroxy-15-methyl-                                                            3,3 dimethyl-13-trans-                                                        prostenoic acid                                        1085    262            9-oxo-15-hydroxy-15-                                                          methyl-3-oxa-13-trans-                                                        prostenoic acid and                                                           9α,15-dihydroxy-15-                                                     methyl-3-oxa-13-trans-                                                        prostenoic acid                                        1086    264            9-oxo-15-hydroxy-15-                                                          methyl-2-fluoro-13-                                                           trans-prostenoic acid                                                         and 9α,15-dihydroxy-                                                    15-methyl-2-fluoro-                                                           13-trans-prostenoic                                                           acid                                                   1087    266            9-oxo-15-hydroxy-15-                                                          methyl-2-phenyl-13-                                                           trans-prostenoic acid                                                         and 9α,15-dihydroxy-                                                    15-methyl-2-phenyl-                                                           13-trans-prostenoic                                                           acid                                                   1088    267            9-oxo-15-hydroxy-15-                                                          methyl-2-methyl-13-                                                           trans-prostenoic acid                                                         and 9α,15-dihydroxy-                                                    15-methyl-2-methyl-                                                           13-trans-prostenoic                                                           acid                                                   1089    268            9-oxo-15-hydroxy-15-                                                          methyl-10α-homo-13-                                                     trans-prostenoic acid                                                         and 9α,15-dihydroxy-                                                    15-methyl-10a-homo-                                                           13-trans-prostenoic                                                           acid                                                   1090    272            9-oxo-15-hydroxy-15-                                                          methyl-3-thia-13-                                                             trans-prostenoic acid                                                         and 9α,15-dihydroxy-                                                    15-methyl-3-thia-13-                                                          trans-prostenoic acid                                  1091    362            9-oxo-15-hydroxy-15-                                                          methyl-3-thia-20-                                                             methyl-13-trans-pro-                                                          stenoic acid and 9α,15-                                                 dihydroxy-15-methyl-3-                                                        thia-20-methyl-13-                                                            trans-prostenoic acid                                  1092    343            9-oxo-15-hydroxy-15-                                                          methyl-2,20-dimethyl-                                                         13-trans-prostenoic                                                           acid and 9α,15-di-                                                      hydroxy-15-methyl-                                                            2,20-dimethyl-13-                                                             trans, prostenoic acid                                 1093    323            9-oxo-15-hydroxy-15-                                                          methyl-3-oxa-20-methyl-                                                       13-trans-prostenoic                                                           acid and 9α,15-di-                                                      hydroxy-15-methyl-3-                                                          oxa-20-methyl-13-                                                             trans-prostenoic acid                                  1094    284            9-oxo-15-hydroxy-15-                                                          methyl-13-trans, 17-                                                          cis-prostadienoic acid                                                        and 9α,15-dihydroxy-15-                                                 methyl-13-trans,17-                                                           cis-prostadienoic acid                                 1095    287            9-oxo-15-hydroxy-15-                                                          methyl-7a, 7b-bishomo-                                                        13-trans, 17-cis-pro-                                                         stadienoic acid and 9α,                                                 15-dihydroxy-15-methyl-                                                       7a, 7b-bishomo-13-                                                            trans, 17-cis-prosta-                                                         dienoic acid                                           1096    290            9-oxo-15-hydroxy-15-                                                          methyl-3-oxa-13-trans,                                                        17-cis-prostadienoic                                                          acid and 9α, 15-dihydro-                                                xy-15-methyl-3-oxa-13-                                                        trans, 17-cis-prosta- -  dienoic acid                  1097    291            9-oxo-15-hydroxy-15-                                                          methyl-7-nor-13-trans                                                         17-cis-prostadienoic                                                          acid and 9α,15-di-                                                      hydroxy-15-methyl-7-                                                          nor-13-trans, 17-cis-                                                         prostadienoic acid                                     1098    292            9-oxo-15-hydroxy-15-                                                          methyl-2-fluoro-13-                                                           trans, 17-cis-prosta-                                                         dienoic acid and 9α,                                                    15-dihydroxy-15-methyl-                                                       2-fluoro-13-trans,                                                            17-cis-prostadienoic                                                          acid                                                   1099    293            9-oxo-15-hydroxy-15-                                                          methyl-7a-homo-13-                                                            trans, 17-cis-prosta-                                                         dienoic acid and 9α,15-                                                 dihydroxy-15-methyl-7a-                                                       homo-13-trans, 17-cis-                                                        prostadienoic acid                                     1100    300            9-oxo-15-hydroxy-15-                                                          methyl-3-thia-13-trans,                                                       17-cis-prostadienoic                                                          acid and 9α, 15-di-                                                     hydroxy-15-methyl-3-                                                          thia-13-trans, 17-cis-                                                        prostadienoic acid                                     1101    733            9-oxo-15-hydroxy-15-                                                          methyl-13-cis, 17-cis-                                                        prostadienoic acid and                                                        9α, 15-dihydroxy-15-                                                    methyl-13-cis, 17-cis                                                         prostadienoic acid                                     ______________________________________                                         *methyl 15hydroxy-9-oxo-13-cis-prostenoate only                          

EXAMPLES 1102-1104

Hydrogenation of the 13-trans-prostenoic acids listed in Table 19 belowby the procedure described in Example 699 is productive of the productprostanoic acids of the table. The product epimers are separable bychromatographic procedures.

                  TABLE 19                                                        ______________________________________                                                Starting 15-hy-                                                               droxy-15-methyl-                                                                             Product 15-hydroxy-                                    Ex-     13-trans-pros- 15-methyl-prostanoic                                   ample   tenoic acid    acid                                                   ______________________________________                                        1102    9-oxo-15-hydroxy-                                                                            9-oxo-15-hydroxy-15-                                           15-methyl-3-oxa-                                                                             methyl-3-oxa-prostanoic                                        13-trans-pros- acid                                                           tenoic acid                                                                   (Example 1085)                                                        1103    9α,15-dihydroxy-                                                                       9α,15-dihydroxy-15-                                      15-methyl-3-oxa-                                                                             methyl-3-oxa-pros-                                             13-trans-pros- tanoic acid                                                    tenoic acid                                                                   (Example 1085)                                                        1104    9-oxo-15-hydroxy-                                                                            9-oxo-15-hydroxy-15-                                           15-methyl-10a- methyl-10a-homo-pros-                                          homo- 13-trans-                                                                              tanoic acid                                                    prostenoic acid                                                               (Example 1089)                                                        ______________________________________                                    

EXAMPLE 1105 Preparation of allcis-2-(6-carboxy-2-cis-hexenyl)-3,4-oxido-cyclopentanol

A solution of 1.42 g. (10.0 moles) ofall-cis-5-hydroxy-2,3-oxidocyclopentylacetaldehyde-lactol (E. J. Coreyand R. Noyori, Tetrahedron Letters, 1970, 311) in 5 ml. of DMSO is addedto a stirred solution with the Whttig reagent [E. J. Corey et al. JACS,91 5675 (1969)] also Example 1108 prepared from 13.3 g. (30 moles) of4-carboxybutyltriphenylphosphonium bromide 2.52 g. (60 moles) of 57%sodium hydride dispersion, and 70 ml. of DMSO at 16° C. during 1 minute.

The solution is stirred at ambient temperature for 20 hours and pouredinto a stirred mixture of methylene chloride, ice, and hydrochloricacid. The organic phase is separated, and the aqueous phase is extractedwith methylene chloride, saturated with sodium chloride, and extractedwith ether. The combined organic extracts are partitioned with sodiumbicarbonate. The aqueous basic extract is acidified with dilute HCl,saturated with sodium chloride, and extracted with ethyl acetate. Theextract is washed with brine, dried over magnesium sulfate, andconcentrated to give the crude title compound as an orange oil.

EXAMPLE 1106 Preparation ofall-cis-2-(6-carboxy-2-cis-hexenyl)-3,4-oxidocyclopentanone

To a stirred solution of ca. 1.6 moles of crudeall-cis-2-(6-carboxy-2-cis-hexenyl)-3,4-oxidocyclopentanol (Example1105) in 1.6 ml. of ether is added 1.6 ml. of 4.0 N chromic acid in 4 Nsulfuric acid at 0° C. during 9 minutes. After stirring for 5 minutes at0° C. the solution is diluted with brine, ether, and ethyl acetate. Theorganic phase is treated with isopropanol, washed with brine and driedover magnesium sulfate. Evaporation of the solvent gives the subjectcompound as an oil.

EXAMPLE 1107 Preparation of2-(6-carboxy-2-cis-hexenyl)-4-hydroxycyclopent-2-en-1-one

A solution of 1.0 mmole ofall-cis-2-(6-carboxy-2-cis-hexenyl)-3,4-oxidocyclopentanone (Example1106) and 3.0 mmoles of sodium carbonate in 15 ml. of water is allowedto stand at room temperature for 3 hours. The solution is acidified withHCl, saturated with sodium chloride, and extracted with ether. Theextract is washed with brine, dried over magnesium sulfate, andconcentrated to give a mixture of the title compound and the isomericcompound, 2-(6-carboxy-2-cis-hexenyl)-3-hydroxycyclopent-4-en-1-one.Further treatment of this mixture with N/10 sodium hydroxide at roomtemperatue for 30 minutes causes the rearrangement of the latter isomerto the title compound, which is isolated from basic solution as above.

EXAMPLE 1107a Preparation of2-(6-carboxy-2-cis-hexenyl)-4-hydroxycyclopent-2-en-1-one

Treatment ofcis-anti-cis-5-hydroxy-2,3-oxidocyclopentylacetaldehyde-γ-lactol (E. J.Corey and R. Noyori Tetrahedron Letters, 1970, 311) with4-carboxybutyltriphenylphosphonium bromide as described in Example 1105is productive of2β-(6-carboxy-2-cis-hexenyl)-3α,4α-oxidocyclopentan-1.beta.-ol which onon oxidation by the method of Example 1106 provides 2β-(6-carboxy-2-cishexenyl)-3α,4α-oxidocyclopentanone, which in time on treatment withaqueous base by the procedure of Example 1107 furnishes the subjectcompound.

EXAMPLE 1108 Preparation of 4-carboxybutyltriphenylphosphonium bromide

A mixture of 103 g. of 5-bromovalevic acid and 152 g. oftriphenylphosphine in 400 ml. of acetonitrile is refluxed for 48 hours,cooled, diluted with 100 ml. of benzene and allowed to crystallize. Thecrystals are filtered, washed with benzene and ether, to yield colorlessmaterial, m.p. 207°-209° C.

EXAMPLES 1109-1111

Treatment of the indicated ω-bromoalkanoic acids of Table 20 below withtriphenylphosphine by the method described in Example 1108 produces thephosphonium bromides of the table.

                  TABLE 20                                                        ______________________________________                                        Ex-     Starting ω-bromo-                                                                       Product                                               ample   alkanone acid   Phosphonium bromide                                   ______________________________________                                        1109    4-bromo-n-butyric                                                                             3-carboxypropyltri-                                           acid            phenylphosphonium                                                             bromide                                               1110    6-bromo-n-hexanoic                                                                            5-carboxypentyltri-                                           acid            phenylphosphonium                                                             bromide                                               1111    7-bromo-n-hepta-                                                                              6-carboxyhexyltri-                                            noic acid       phenylphosphonium                                                             bromide                                               ______________________________________                                    

EXAMPLES 1112-1114

Treatment of all cis-5-hydroxy-2,3-oxidocyclopentylacetaldehyde-γ-lactolwith the Wittig reagent prepared from the indicated phosphonium bromidesof Table 21 below, all by the procedure of Example 1105 is productive ofthe product compounds of the table.

                  TABLE 21                                                        ______________________________________                                                Reagent phos-                                                         Ex-     phonium bromide Product                                               ample   of Example      3,4-oxidocyclopentanol                                ______________________________________                                        1112    1109            all cis-2-(5-carboxy-2-                                                       cis-peptenyl)-3,4-oxi-                                                        docyclopentan-1-ol                                    1113    1110            all cis-2-(7-carboxy-2-                                                       cis-heptenyl)-3,4-oxi-                                                        docyclopentan-1-ol                                    1114    1111            all cis-2-(8-carboxy-2-                                                       cis-octenyl)-3,4-oxi-                                                         docyclopentan-1-ol                                    ______________________________________                                    

EXAMPLES 1115-1117

Oxidation of the cyclopentanols indicated in Table 22 below by themethod described in Example 1106 furnishes the corresponding product3,4-oxidocyclopentanones of the table.

                  TABLE 22                                                        ______________________________________                                                Starting cyclo-  Product                                              Ex-     pentan-1-ol of   3,4-oxidocyclopent-                                  ample   Example          an-1-one                                             ______________________________________                                        1115    1112             all cis-2-(5-carboxy-                                                         2-cis-pentenyl)-3,4-                                                          oxidocyclopentan-1-                                                           one                                                  1116    1113             all cis-2-(7-carboxy-                                                         2-cis-heptenyl)-3,4-                                                          oxidocyclopentan-1-                                                           one                                                  1117    1114             all cis-2-(8-carboxy-                                                         2-cis-octenyl)-3,4-                                                           oxidocyclopentan-1-                                                           one                                                  ______________________________________                                    

EXAMPLES 1118-1120

Alkaline treatment of the 3,4-oxidocyclopentanones of Table 23 below bythe process described in Example 1107 is productive of the4-hydroxycyclopentenones of the table.

                  TABLE 23                                                        ______________________________________                                                 Starting 3,4-                                                                 oxidocyclo-      Product                                             Ex-      pentanone of     4-hydroxycyclo-                                     ample    Example          pent-2-en-1-one                                     ______________________________________                                        1118     1115             2-(5-carboxy-2-                                                               cis-pentenyl)-4-                                                              hydroxycyclo-                                                                 pent-2-en-1-one                                     1119     1116             2-(7-carboxy-2-                                                               cis-heptenyl)-                                                                4-hydroxycyclo-                                                               pent-2-en-1-one                                     1120     1117             2-(8-carboxy-2-                                                               cis-octenyl)-4-                                                               hydroxycyclo-                                                                 pent-2-en-1-one                                     ______________________________________                                    

EXAMPLES 1121-1124

Treatment of the 4-hydroxycyclopent-2-en-1-ones listed in Table 24 belowwith dihydropyran is productive of the correspondingbis-tetrahydropyranyl ether-ester of the table.

                  TABLE 24                                                        ______________________________________                                                Starting 4-hy-                                                                droxycyclopent-                                                                             Product                                                 Ex-     2-en-1-one of bis-tetrahydropyranyl                                   ample   Example       ether-ester                                             ______________________________________                                        1121    1107          4-tetrahydropyranyloxy-                                                       2-(6-carbotetrahydro-                                                         pyranyloxy-2-cis-hexenyl)                                                     cyclopent-2-en-1-one                                    1122    1118          4-tetrahydropyranyloxy-                                                       2-(5-carbotetrahydro-                                                         pyranyloxy-2-cis-pent-                                                        enyl)cyclopent-2-en-1-                                                        one                                                     1123    1119          4-tetrahydropyranyloxy-                                                       2-(7-carbotetrahydro-                                                         pyranyloxy-2-cis-heptenyl)-                                                   cyclopent-2-en-1-one                                    1124    1120          4-tetrahydropyranyloxy-                                                       2-(8-carbotetrahydro-                                                         pyranyloxy-2-cis-octenyl)-                                                    cyclopent-2-en-1-one                                    ______________________________________                                    

EXAMPLES 1125-1130

Treatment of the 4-hydroxycyclopent-2-en-1-ones listed in Table 25 belowwith the indicated trialkylsilyl chloride by the method described inExample 958 is productive of the bis-trialkylsilyl ether-esters of thetable.

                                      TABLE 25                                    __________________________________________________________________________         Starting 4-hydroxy-                                                           cyclopentenone of                                                                       Trialkylsilyl-                                                                       Product                                                 Example                                                                            Example   chloride                                                                             bis-trialkylsilyl ether-ester                           __________________________________________________________________________    1125 1107      (CH.sub.3).sub.3 SiCl                                                                4-trimethylsiloxy-2-(6-carbotrimethyl-                                        siloxy-2-cis-hexenyl)cyclopent-2-en-1-one               1126 1118      (CH.sub.3).sub.3 SiCl                                                                4-trimethylsiloxy-2-(5-carbotrimethyl-                                        siloxy-2-cis-pentenyl)cyclopent-2-en-1-one              1127 1119      (CH.sub.3).sub.3 SiCl                                                                4-trimethylsiloxy-2-(7-carbotrimethyl-                                        siloxy-2-cis-heptenyl)cyclopent-2-en-1-one              1128 1120      (CH.sub.3).sub.3 SiCl                                                                4-trimethylsiloxy-2-(8-carbotrimethyl-                                        siloxy-2-cis-octenyl)cyclopent-2-en-1-one               1130 1107      dimethyliso-                                                                         4-dimethylisopropylsiloxy-2-(6-carbodi-                                propyl silyl                                                                         methylisopropylsiloxy-2-cis-hexenyl)cyclo-                             chloride                                                                             pent-2-en-1-one                                         __________________________________________________________________________

EXAMPLE 1131 Preparation of 1-oxo-2-hydroxy-bicyclo[3.3.0]oct-4-ene

A solution of 6.2 g. (50 mole) of the lactone ofcis-2-hydroxycyclopent-4-ene-1-acetic acid [P.A. Grieco, J. Org. Chem.,37, 2363 (1972)] in 350 ml. toluene (dried over molecular sieves) iscooled to -75° C. and treated dropwise under nitrogen with 84 ml. 0.89 Mdiisobutyl aluminum hydride (10.55 g., 74 mole) over a period of aboutone hour maintaining the temperature at -74±2° C. The resulting clearsolution is stirred at -75° C. for two hours and poured with stirringinto a mixture of 15 ml. of concentrated hydrochloric acid and 300 ml.of ice water. The mixture is stirred while warming to room temperature.The layers are separated and the aqueous layer is treated with salt andextracted with three small portions of ether. The combined organicportions are dried over sodium sulfate and evaporated at reducedpressure (75° C. water bath) to yield the product (homogeneous by thinlayer chromatography) as a pale yellow mobile liquid.

EXAMPLE 1132 Preparation of1-hydroxy-2-(6-carboxy-2-cis-hexenyl)cyclopent-3-ene

A solution of the sodium salt of dimethyl sulfoxide is prepared bystirring under nitrogen a mixture of 160 ml. dry dimethyl sulfoxide(dried over molecular sieves and a few pellets of calcium hydride) with6.0 g. (0.25 mole) of sodium hydride (prepared by washing 10.5 g. of 57%sodium hydride dispersion in mineral oil with two 30 ml. portions ofhexane.) The mixture is warmed with stirring at 75° C. (oil bath) for2.5 hours.

This solution is added over about five minutes to a solution undernitrogen of 44 grams (0.1 mole) of 4-carboxybutyltriphenylphosphoniumbromide (Example 1108) in 180 ml. of dry dimethyl sulfoxide. Theresulting dark reddish brown solution is stirred for ten minutes, cooledto room temperature and treated with a solution of crude1-oxa-2-hydroxy-bicyclo[3.3.0]oct-4-ene (6.2 g., 50 mole) (Example 1131)in 20 ml. of anhydrous dimethyl sulfoxide. The resulting solution isstirred 16 hours and then treated with 250 ml. of ice water.

This brown solution is extracted with two portions of ether to removeneutral material then made strongly acidic with hydrochloric acid. Thesolution is extracted into four 100 ml. portions of methylene chloride.The combined methylene chloride extracts are washed with water, thenextracted with four 100 ml. portions of 5% sodium bicarbonate. Thecombined aqueous extracts are washed with methylene chloride and madeacidic to Congo Red with concentrated hydrochloric acid. The mixture isextracted with three 100 ml. portions of methylene chloride. The organicextracts are combined, dried over sodium sulfate and the solvent isevaporated at reduced pressure. The residue (an oily solid) is extractedseveral times with ether and the ethereal extracts are combined andevaporated at reduced pressure to yield the crude product as a dark oil.The product is purified by chromatographs on silica gel, eluting withether. The product is a colorless liquid.

EXAMPLE 1133 Preparation of2-(6-carboxy-2-cis-hexenyl)cyclopent-3-en-1-one

A solution of 3.2 g. (0.5 mole) of1-hydroxy-2-(6-carboxy-2-cis-hexenyl)cyclopent-3-ene (Example 1132) in60 ml. of reagent acetone is treated dropwise with a total of 6 ml. of 8N chromic acid in sulfuric acid at 0° C. The oxidation is rather slow.The resulting mixture is dissolved in 200 ml. of water and the solutionis extracted with six 50 ml. portions of ether. The combined etherealextracts are dried over sodium sulfate and the solvent is evaporated atreduced pressure to yield the product as a yellow oil.

EXAMPLE 1134 Preparation of2-(6-carboxy-2-cis-hexenyl)cyclopent-2-en-1-one

A solution of 3 g. of crude2-(6-carboxy-2-cis-hexenyl)cyclopent-3-en-1-one (Example 1133) in 100ml. of 2% sodium hydroxide is stirred at 80° C. under nitrogen for 1.5hours. The cooled solution is acidified to Congo Red and extracted intoether. The ethereal extracts are dried over sodium sulfate andevaporated at reduced pressure to afford the product.

EXAMPLES 1135-1137

Treatment of 1-oxa-2-hydroxy-bicyclo[3.3.0]oct-4-ene by the proceduredescribed in Example 1132 with the ylids derived from the phosphoniumbromides listed in Table 26 below furnishes the product1-hydroxy-cyclopent-3-enes of the table.

                  TABLE 26                                                        ______________________________________                                                               Product                                                        Starting phos- 1-hydroxy-2-(ω-carboxy-                          Ex-     phonium bromide                                                                              2-cis-alkenyl)cyclopent-                               ample   of Example     3-enes                                                 ______________________________________                                        1135    1109           1-hydroxy-2-(5-carboxy-                                                       2-cis-pentenyl)cyclo-                                                         pent-3-ene                                             1136    1110           1-hydroxy-2-(7-carboxy-                                                       2-cis-heptenyl)cyclo-                                                         pent-3-ene                                             1137    1111           1-hydroxy-2-(8-carboxy-                                                       2-cis-octenyl)cyclo-                                                          pent-3-ene                                             ______________________________________                                    

EXAMPLES 1138-1140

Oxidation of the 1-hydroxycyclopent-3-enes listed in Table 27 below bythe procedure described in Example 1133 is productive of the productcyclopent-3-en-1-ones of the table.

                  TABLE 27                                                        ______________________________________                                                Starting 1-     Product                                                       hydroxycyclo-   2-(ω-carboxy-2-cis-                             Ex-     pent-3-ene of   alkenyl)cyclopent-3-                                  ample   Example         en-1-one                                              ______________________________________                                        1138    1135            2-(5-carboxy-2-cis-                                                           pentenyl)cyclopent-3-                                                         en-1-one                                              1139    1136            2-(7-carboxy-2-cis-                                                           heptenyl)cyclopent-3-                                                         en-1-one                                              1140    1137            2-(8-carboxy-2-cis-                                                           octenyl)cyclopent-3-                                                          en-1-one                                              ______________________________________                                    

EXAMPLES 1141-1143

Base treatment according to the procedure described in Example 1134 ofthe cyclopent-3-ene-1-ones listed in Table 28 below is productive of theproduct cyclopent-2-en-1-ones of the table.

                  TABLE 28                                                        ______________________________________                                                Starting 2-(ω-                                                          carboxy-2-cis-   Product                                                      alkenyl)cyclo-   2-(ω-carboxy-2-cis-                            Ex-     pent-3-ene-1-    alkenyl)cyclopent-                                   ample   one of Example   2-en-1-one                                           ______________________________________                                        1141    1138             2-(5-carboxy-2-cis-                                                           pentenyl)cyclopent-                                                           2-en-1-one                                           1142    1139             2-(7-carboxy-2-cis-                                                           heptenyl)cyclopent-                                                           2-en-1-one                                           1143    1140             2-(8-carboxy-2-cis-                                                           octenyl)cyclopent-                                                            en-en-1-one                                          ______________________________________                                    

EXAMPLES 1144-1146

Treatment of the listed 2-(ω-carboxy-2-cis-alkenyl)cyclopent-2-en-1-oneof Table 29 below with diazomethane in the usual manner is productive ofthe product methyl esters of the table.

                  TABLE 29                                                        ______________________________________                                                               Product                                                        Starting car-  2-(ω-carbomethoxy-2-cis-                         Ex-     boxylic acid   alkenyl)cyclopent-2-en-                                ample   of Example     1-one                                                  ______________________________________                                        1144    1141           2-(5-carbomethoxy-2-cis-                                                      pentenyl)cyclopent-2-en-                                                      1-one                                                  1145    1142           2-(7-carbomethoxy-2-cis-                                                      heptenyl)cyclopent-2-en-                                                      1-one                                                  1146    1143           2-(8-carbomethoxy-2-cis-                                                      octenyl)cyclopent-2-en-                                                       1-one                                                  ______________________________________                                    

EXAMPLES 1147-1149

Treatment by the procedure of Example 120 of the cyclopentenones listedin Table 30 below with lithiumdiisobutylmethyl-(3-triphenylmethoxy-1-trans-5-cis-octadienyl) alanate,also prepared by the procedure of Example 120 from3-triphenylmethoxy-cis-5-en-octyne-1 (Example 139), diisobutylaluminumhydride and methyl lithium, followed by hydrolysis of the intermediate15-triphenylmethoxy derivatives by treatment with aceticacid-tetrahydrofuran-water (4:2:1) in the manner of Example 121, andthey by saponification of the intermediate methyl esters by the processdescribed in Example 122 is productive of the product prostatrienoicacids of the table.

                  TABLE 30                                                        ______________________________________                                                Starting 2-(ω-                                                          carbomethoxy-2-                                                                              Product                                                        cis-alkenyl)-  9-oxo-15-hydroxy-5-                                    Ex-     cyclopent-2-en-                                                                              cis,13-trans,17-cis-                                   ample   1-one of Example                                                                             prostatrienoic acids                                   ______________________________________                                        1147    1144           9-oxo-4-nor-15-hydroxy-                                                       5-cis-13-trans-17-                                                            cis-prostatrienoic                                                            acid                                                   1148    1145           9-oxo-4a-homo-15-hydro-                                                       xy-5-cis-13-trans-17-                                                         cis-prostatrienoic                                                            acid                                                   1149    1146           9-oxo-4a-bishomo-15-hy-                                                       droxy-5-cis-13-trans-                                                         1-cis-prostatrienoic                                                          acid                                                   ______________________________________                                    

EXAMPLES 1150-1159

Treatment of the ether-ester blocked 4-oxycyclopent-2-en-1-ones listedin Table 31 below with lithiumtrimethyl[3-(p-anisyldiphenylmethoxy)-trans-1-octenyl] according to theprocedure described in Example 960 is productive of the9-oxo-11α,15-dihydroxy-5-cis,13-trans-prostadienoic acids of the tableas well as of the corresponding 15-epi derivatives, separable from thelisted 15-normal derivatives by chromatography.

                  TABLE 31                                                        ______________________________________                                                Starting blocked                                                                              Product                                                       4-oxycyclopent- 9-oxo-11α,15-dihydroxy-                         Ex-     2-en-1-one of   5-cis,13-trans-pros-                                  ample   Example         tadienoic acids                                       ______________________________________                                        1150    1121            9-oxo-11α,15-dihydroxy-                                                 5-cis,13-trans-prosta-                                                        dienoic acid (prosta-                                                         glandin E.sub.2)                                      1151    1125            9-oxo-11α,15-dihydroxy-                                                 5-cis,13-trans-prosta-                                                        dienoic acid (prosta-                                                         glandin E.sub.2)                                      1152    1130            9-oxo-11α,15-dihydroxy-                                                 5-cis,13-trans-prosta-                                                        dienoic acid (prosta-                                                         glandin E.sub.2)                                      1153    1122            9-oxo-11α,15-dihydroxy-                                                 4-nor-5-cis,13-trans-                                                         prostadienoic acid                                    1154    1126            9-oxo-11α,15-dihydroxy-                                                 4-nor-5-cis,13-trans-                                                         prostadienoic acid                                    1155    1123            9-oxo-11α,15-dihydroxy-                                                 4a-homo-5-cis,13-trans-                                                       prostadienoic acid                                    1156    1127            9-oxo-11a ,15-dihydroxy-                                                      4a-homo-5-cis,13-trans-                                                       prostadienoic acid                                    1158    1124            9-oxo-11α,15-dihydroxy-                                                 4a,4b-homo-5-cis,13-                                                          trans-prostadienoic                                                           acid                                                  1159    1128            9-oxo-11α,15-dihydroxy-                                                 4a,4b-homo-5-cis,13-                                                          trans-prostadienoic                                                           acid                                                  ______________________________________                                    

EXAMPLES 1160-1169

Treatment by the procedure described in Example 123 of the ether-esterblocked 4-oxycyclopent-2-en-1-ones listed in Table 32 below with lithiumdiisobutylmethyl(3-triphenylmethoxy-1-trans-5-cis-octadienyl)alanate,prepared from 3-triphenylmethoxy-cis-5-en-octyne-1- (Example 139) by theprocedure of Example 120, followed by the cleavage of blocking groupsand isolation of products by the method described in Example 124 isproductive of the9-oxo-11α,15-dihydroxy-5-cis,13-trans,17-cis-prostatrienoic acids of thetable; also formed are the corresponding 15-epi derivatives which areseparable by chromatography from the listed 15-normal derivatives.

                  TABLE 32                                                        ______________________________________                                                Starting blocked                                                                              Product                                                       4-oxycyclopent- 9-oxo-11α,15-dihydroxy-                         Ex-     2-en-1-one of   5-cis,13-trans,17-cis-                                ample   Example         prostatrienoic acids                                  ______________________________________                                        1160    1121            9-oxo-11α,15-dihydroxy-                                                 5-cis,13-trans,17-                                                            cis-prostatrienoic                                                            acid (prostaglandin E.sub.3)                          1161    1125            9-oxo-11α,15-dihydroxy-                                                 5-cis,13-trans,17-cis-                                                        prostatrienoic acid                                                           (prostaglandin E.sub.3)                               1162    1130            9-oxo-11α,15-dihydroxy-                                                 5-cis,13-trans,17-cis-                                                        prostatrienoic acid                                                           (prostaglandin E.sub.3)                               1163    1122            9-oxo-11α,15-dihydroxy-                                                 4-nor-5-cis,13-trans,                                                         17-cis-prostatrienoic                                                         acid                                                  1164    1126            9-oxo-11α,15-dihydroxy-                                                 4-nor-5-cis,13-trans,                                                         17-cis-prostatrienoic                                                         acid                                                  1165    1123            9-oxo-11α,15-dihydroxy-                                                 4a-homo-5-cis,13-                                                             trans,17-cis-prosta-                                                          trienoic acid                                         1166    1127            9-oxo-11α,15-dihydroxy-                                                 4a-homo-5-cis,13-                                                             trans,17-cis-prosta-                                                          trienoic acid                                         1168    1124            9-oxo-11α,15-dihydroxy-                                                 4a,4b-bishomo-5-cis,                                                          13-trans,17-cis-prosta-                                                       trienoic acid                                         1169    1128            9-oxo-11α,15-dihydroxy-                                                 4a,4b-bishomo-5-cis-                                                          13-trans,17-cis-prosta-                                                       trienoic acid                                         ______________________________________                                    

EXAMPLE 1170 Preparation of9-oxo-11α,15-dihydroxy-5-cis,13-cis-prostadienoic acid

Treatment in the manner described in Example 733 of4-tetrahydropyranyloxy-2-(6-carbotetrahydropyranyloxy-2-cis-hexenyl)cyclopent-2-en-1-one(Example 1121) with the Grignard reagent prepared from magnesium and1-bromo-3-triphenylmethoxy-trans-1-octene (Example 728) also asdescribed in Example 733 in the presence of cuprous iodidetri-n-butylphosphine complex is productive after chromatography ofprostaglandin E₂ and 9-oxo-11α,15-dihydroxy-5-cis,13-cis-prostadienoicacid.

EXAMPLES 1171 AND 1172

Treatment of the two 9-oxo derivative listed in Table 33 below withlithium perhydro-9b-boraphenalylhydride in the manner described inExample 737 furnishes the indicated 9α,15-dihydroxy-13-cis-prostenoicacids.

                  TABLE 33                                                        ______________________________________                                                Starting 9-oxo-                                                                              Product                                                Ex-     derivative of  9α,15-dihydroxy-13-cis-                          ample   Example        prostenoic acids                                       ______________________________________                                        1171     736           9α,15-dihydroxy-13-cis-                                                 prostenoic acid                                        1172    1170           9α,15-dihydroxy-5-cis-                                                  prostadienoic acid                                     ______________________________________                                    

EXAMPLE 1173 Preparation of1-bromo-4,4-dimethyl-3-tetrahydropyranyloxy-trans-1-octene

To an ice cooled solution of 3.5 g. (50 moles) of 2-methyl-2-butene in25 ml. of tetrahydrofuran under an inert atmosphere is added 25 ml. of 1M diborane in tetrahydrofuran dropwise over 10 minutes. The mixture isstirred at 0°-5° C. for 2 hours and then the solvent is removed undervacuum. The residue is dissolved in 20 ml. of carbon tetrachloride andto the resulting solution cooled to 0° C. is added a solution of 5.25 g.(22 moles) of 4,4-dimethyl-3-tetrahydropyranyloxy-1-octyne (Example 995)in 10 ml. of carbon tetrachloride over 10 minutes. The cooling bath isremoved and the mixture is allowed to stir at ambient temperature for1.5 hours. The mixture is cooled to 0° C. and a solution of 3.52 g. (22moles) of bromine in 15 ml. of carbon tetrachloride is added over 10minutes. The cooling bath is removed and the mixture is refluxed for 6hours under an inert atmosphere. The mixture is cooled and poured intodilute sodium hydroxide solution. The organic phase is washed with waterand saturated brine, dried (Na₂ SO₄), and evaporated. The residue ischromatographed upon silica gel and the title compound is isolated with5% ethyl acetate in benzene.

EXAMPLE 1174 Preparation of 1-bromo-4,4-dimethyl-trans-1-octen-3-ol

A mixture of 3.19 g. (10 moles) of1-bromo-4,4-dimethyl-3-tetrahydropyranyloxy-trans-1-octene (Example1173) and 90 ml. of 3:1:1 tetrahydrofuran-acetic acid-water is stirredat ambient temperatures for 20 hours. The solvent is evaporated in vacuoand the residue is chromatographed on silica gel. The title compound isisolated using 10-20% ethyl acetate in benzene.

EXAMPLE 1175 Preparation of1-bromo-4,4-dimethyl-3-triphenylmethoxy-trans-1-octene

Treatment of 1.88 g. (8 moles) of1-bromo-4,4-dimethyl-trans-1-octen-3-ol (Example 1174) with 2.58 g. (8moles) of triphenylmethyl bromide in 20 ml. of pyridine and purificationof Florisil®, all as described in Example 728 gives the title compound.

EXAMPLE 1176 Preparation of1-bromo-5,5-dimethyl-3-tetrahydropyranyloxy-trans-1-octene

Treatment of 7.15 g. (30 moles) of5,5-dimethyl-3-tetrahydropyranyloxy-1-octyne (Example 999) with 33 molesof disiamylborane in carbon tetrachloride followed by 30 moles ofbromide in carbon tetrachloride, refluxing the resulting mixture, andisolation by chromatography on silica gel, all as described in Example1173 gives the title compound.

EXAMPLE 1177 Preparation of 1-bromo-5,5-dimethyl-trans-1-octen-3-ol

Treatment of 7.35 g. (23 moles) of1-bromo-5,5-dimethyl-3-tetrahydropyranyloxy-trans-1-octene (Example1176) with 200 ml. of 3:1:1 tetrahydrofuran-acetic acid-water andpurification on silica gel all as described in Example 1174 gives thetitle compound.

EXAMPLE 1178 Preparation of1-bromo-5,5-dimethyl-3-triphenylmethoxy-trans-1-octene

Treatment of 3.53 g. (15 moles) of1-bromo-5,5-dimethyl-trans-1-octen-3-ol (Example 1177) with 4.85 g. (15moles) of triphenylmethyl bromide in 35 ml. of pyridine and purificationof Florisil®, all as described in Example 728 gives the title compound.

EXAMPLE 1179 Preparation of 1-iodo-3-triphenylmethoxy-trans-1-octene

To a mixture of 0.650 g. (16.91 mole) of sodium borohydride and 3.17 g.(45.2 moles) of 2-methyl-2-butene in 40 ml. of diglyme cooled to -5° C.under an inert atmosphere is added over 15 minutes 3.24 g. (22.6 moles)of boron trifluoride ethereate and the resulting mixture is stirred at0° C. for 2 hours. To this mixture is then added over 5 minutes 8.32 g.(22.6 moles) of 3-triphenylmethoxy-1-octyne (Example 119) in 10 ml. ofdiglyme, the cooling bath is removed, and the mixture is stirred atambient temperatures for 1.5 hours. The mixture is cooled to 0° C. and6.0 g. of finely divided anhydrous trimethylamine oxide is added over 10minutes. The cooling bath is removed and the mixture is stirred atambient temperatures for 0.5 hour. The mixture is then poured into 200ml. of 15% sodium hydrooxide solution, a solution of 16 g. (83 moles) ofiodine in 20 ml. of tetrahydrofuran is added immediately, and theresulting mixture is stirred for 0.5 hour. The organic phase isseparated and the aqueous phase is washed with ether. The combinedorganic phase and washings are decolorized with 5% sodium thiosulfatesolution, washed with saturated brine, dried (Na₂ SO₄), and evaporated.The residue is dry-columned chromatographed upon alumina using hexane aseluent and the title compound is isolated as an oil.

EXAMPLE 1180 Preparation of 3-triphenylmethoxy-cis-oct-5-en-1-yne

Treatment of 22 g. of cis-oct-5-en-1-yne-3-ol, prepared according to theprocedure of J. Fried, C. H. Lin, J. C. Sih, P. Dalven, G. F. Cooper, J.Amer. Chem. Soc., 94, 4342 (1972), with 58 g. of triphenylmethyl bromidein 100 ml. of pyridine and purification on Florisil®, all as describedin Example 728 gives the title compound.

EXAMPLE 1181 Preparation of1-iodo-3-triphenylmethoxy-trans-1,cis-5-octadiene

Treatment of 20 g. of 3-triphenylmethoxy-cis-oct-5-en-1-yne with 55moles of disiamylborane in diglyme, followed by trimethylamine oxide,aqueous sodium hydroxide, and iodine, and purification of alumina, allas described in Example 1179, gives the title compound.

EXAMPLE 1182 Preparation of1-bromo-3-triphenylmethoxy-trans-1,cis-5-octadiene

Treatment of 15 g. of 3-triphenylmethoxy-cis-oct-5-en-1-yne (Example1180) with 41 moles of disiamylborane in tetrahydrofuran, replacing thesolvent with carbontetrachloride, addition of 41 moles of brimine, andrefluxing the mixture, all as described in Example 1173, andpurification of the material upon Florisil® as described in Example 728gives the title compound.

EXAMPLE 1183 Preparation of 1-iodo-3-triphenylmethoxy-trans-1-decene

Treatment of 3-triphenylmethoxy-1-decyne (Example 129) withdisamylborane, trimethylamine oxide and iodine by the proceduredescribed in Example 1179 is productive of the subject compound.

EXAMPLE 1184 Preparation of 1-iodo-3-triphenylmethoxy-trans-1-nonene

Treatment of 3-triphenylmethoxy-1-nonyne (Example 128) withdisiamylborane, trimethylamine oxide and iodine by the process describedin Example 1179 is productive of the subject compound.

EXAMPLE 1185 Preparation of 1-bromo-3-triphenylmethoxy-trans-1-decene

Treatment of 3-triphenylmethoxy-1-decyne (Example 129) withdisiamylborane and the bromide by the procedure described in Example1173 is productive of the title compound.

EXAMPLE 1186 Preparation of 1-bromo-3-triphenylmethoxy-trans-1-nonene

Treatment of 3-triphenylmethoxy-1-nonyne (Example 128) withdisiamylborane and the bromine by the procedure described in Example1173 is productive of the title compound.

EXAMPLE 1187 Preparation of the Grignard reagent of1-bromo-3-triphenylmethoxy-trans-1-octene at 33° C.

To a slurry of 0.585 g. (0.0241 g. atom) of magnesium and 5 ml. oftetrahydrofuran under an argon atmosphere is added 2 ml. of a solutionof 7.536 (0.0168 mole) of 1-bromo-3-triphenylmethoxy-trans-1-octene(Example 728) in 10 ml. of tetrahydrofuran. The mixture is warmed to 35°C. and reaction is initiated with 1 drop of methyl iodide. The reactionis allowed to exotherm to 37° C. and then to cool to 33° C. whereuponthe remainder of the halide is added at a rate to maintain 33° C. Aftercomplete addition of the halide, the mixture is stirred at 33° C. for 1hour and is separated from the excess magnesium to yield atetrahydrofuran solution of the title Grignard reagent.

EXAMPLE 1188 Preparation of 11-deoxy-8β-methyl-prostaglandin E₁ methylester, 11-deoxy-8α-methyl-8-iso-prostaglandin E₁ methyl ester, methyl15-hydroxy-8β -methyl-9-oxo-13-cis-prostenoate, and methyl15-hydroxy-8α-methyl-9-oxo-8-iso-13-cis-prostenoate

The Grignard reagent, prepared as described in Example 1187 from 0.585g. of magnesium, 7.536 g. of 1-bromo-3-triphenylmethoxy-trans-1-octene(Example 728), and 10 ml. of tetrahydrofuran, is added to an ice cooledsolution of 3.76 g. of 2-(6-carbomethoxyhexyl)-2-cyclopentenone (Example83) and 0.305 g. of copper (I) iodide-tri-n-butylphosphine complex in 10ml. of tetrahydrofuran over 10 minutes under an inert atmosphere. Themixture is stirred with cooling for 0.5 hour and to it is then added 46g. of methyl iodide. The cooling bath is removed and the mixture isstirred at ambient temperatures for 48 hours. The mixture is poured intosaturated ammonium chloride solution and is extracted into ether. Theorganic phase is washed with saturated brine and is evaporated. Theresidue is heated to 80° C. with 100 ml. of 80% aqueous acetic acid for0.5 hour and the mixture is then evaporated to dryness. The residue isdry-column chromatography upon silica gel using 4:1 benzene-ethylacetate as eluent to afford a mixture of11-deoxy-8β-methyl-prostaglandin E₁ methyl ester and 11-deoxy-8α-methyl-8-iso-prostaglandin E₁ methyl ester and a mixture of methyl15-hydroxy-8β-methyl-9-oxo-13-cis-prostenoate and methyl15-hydroxy-8α-methyl-9-oxo-8-iso-13-cis-prostenoate. Further separationof the 8β and 8α isomers is accomplished by a combination of partitionchromatography and thin layer chromatography.

EXAMPLES 1190-1205

Treatment by the procedure of Example 1188 of the cyclopentenones listedin Table 34 below with the Grignard reagent, prepared as described inExample 1187 from the listed 1-bromo-3-triphenylmethoxy-1-trans-alkenes,and then with methyl iodide furnishes the product 8α and 8β methylprostenoates of the table. The products are all obtained via thecorresponding 15-O-triphenylmethyl derivatives, which are hydrolyticallycleaved as described in Example 1188.

                                      TABLE 34                                    __________________________________________________________________________                    Starting 1-bromo-3-                                                           triphenylmethoxy-1-                                                Starting cycloalkenene                                                                   trans-alkene of                                               Example                                                                            of Example Example   Product 8-alkyl prostenoates                        __________________________________________________________________________    1190 13         1175      ethyl 8-β-methyl-9-oxo-15-hydroxy-16,16-                                 dimethyl-13-trans-prostenoate                                                 ethyl 8α-methyl-9-oxo-15-hydroxy-16,16-                                 dimethyl-8-iso-13-trans-prostenoate                                           ethyl 8β-methyl-9-oxo-15-hydroxy-16,16-                                  dimethyl- 13-cis-prostenoate                                                  ethyl 8α-methyl-9-oxo-15-hydroxy-16,16-                                 dimethyl-8-iso-13-cis-prostenoate                   1191 13         1178      ethyl 8β-methyl-9-oxo-15-hydroxy-17,17-                                  dimethyl-13-trans-prostenoate                                                 ethyl 8α-methyl-9-oxo-15-hydroxy-17,17-                                 dimethyl-8-iso-13-trans-prostenoate                                           ethyl 8β-methyl-9-oxo-15-hydroxy-17,17-                                  dimethyl-13-cis-prostenoate                                                   ethyl 8α-methyl-9-oxo-15-hydroxy-17,17-                                 dimethyl-8-iso-13-cis-prostenoate                   1192 13         1182      ethyl 8β-methyl-9-oxo-15-hydroxy-13-trans,                               N                                                                             17-cis-prostadienoate                                                         ethyl 8α-methyl-9-oxo-15-hydroxy-8-iso-13-                              O                                                                             trans,17-cis-prostadienoate                                                   ethyl 8β-methyl-9-oxo-15-hydroxy-13-cis,                                 17-cis-prostadienoate                                                         ethyl 8α-methyl-9-oxo-15-hydroxy-8-iso-                                 13-cis, 17-cis-prostadienoate                       1193 13         1185      ethyl 8β-methyl-9-oxo-15-hydroxy-20-ethyl-                               13-trans-prostenoate                                                          ethyl 8α-methyl-9-oxo-15-hydroxy-20-ethyl-                              8-iso-13-trans-prostenoate                                                    ethyl 8β-methyl-9-oxo-15-hydroxy-20-ethyl-                               13-cis-prostenoate                                                            ethyl 8α-methyl-9-oxo-15-hydroxy-8-iso-20-                              ethyl-13-cis-prostenoate                            1194 84         1186      decyl 8β-methyl-9-oxo-15-hydroxy-20-                                     methyl-13-trans-prostenoate                                                   decyl 8α-methyl-9-oxo-15-hydroxy-20-                                    methyl-8-iso-13-trans-prostenoate                                             decyl 8β-methyl-9-oxo-15-hydroxy-20-                                     methyl-13-cis-prostenoate                                                     decyl 8α-methyl-9-oxo-15-hydroxy-20-                                    methyl-8-iso-13-cis-prostenoate                     1195 23          728      ethyl 8β-methyl-9-oxo-15-hydroxy-7a,7b-                                  bishomo-13-trans-prostenoate                                                  ethyl 8α-methyl-9-oxo-15-hydroxy-7a,7b-                                 bishomo-8-iso-13-trans-prostenoate                                            ethyl 8β-methyl-9-oxo-15-hydroxy-7a,7b-                                  bishomo-13-cis-prostenoate                                                    ethyl 8α-methyl-9-oxo-15-hydroxy-7a,7b-                                 bishomo-8-iso-13-cis-prostenoate                    1196 31         1185      ethyl 8β-methyl-9-oxo-15-hydroxy-2,20-                                   bisethyl-13-trans-prostenoate                                                 ethyl 8α-methyl-9-oxo-15-hydroxy-2,20-                                  bisethyl-8-iso-13-trans-prostenoate                                           ethyl 8β-methyl-9-oxo-15-hydroxy-2,20-                                   bisethyl-13-cis-prostenoate                                                   ethyl 8α-methyl-9-oxo-15-hydroxy-2,20-                                  bisethyl-8-iso-13-cis-prostenoate                   1197 46         1175      ethyl 8β-methyl-9-oxo-15-hydroxy-3-oxa-16,                               16-dimethyl-13-trans-prostenoate                                              ethyl 8α-methyl-9-oxo-15-hydroxy-3-oxa-16,                              N                                                                             16-dimethyl-8-iso-13-trans-prostenoate                                        ethyl 8β-methyl-9-oxo-15-hydroxy-3-oxa-16,                               O                                                                             16-dimethyl-13-cis-prostenoate                                                ethyl 8α-methyl-9-oxo-15-hydroxy-3-oxa-16,                              16-dimethyl-8-iso-13-cis-prostenoate                1198 46         1182      ethyl 8β-methyl-9-oxo-15-hydroxy-3-oxa-                                  13-trans,17-cis-prostadienoate                                                ethyl 8α-methyl-9-oxo-15-hydroxy-3-oxa-                                 8-iso-13-trans,17-cis-prostadienoate                                          ethyl 8β-methyl-9-oxo-15-hydroxy-3-oxa-                                  13-cis,17-cis-prostadienoate                                                  ethyl 8α-methyl-9-oxo-15-hydroxy-3-oxa-                                 8-iso-13-cis,17-cis-prostadienoate                  1199 53         1186      ethyl 8β -methyl-9-oxo-15-hydroxy-7-nor-                                 20-methyl-13-trans-prostenoate                                                ethyl 8α-methyl-9-oxo-15-hydroxy-7-nor-                                 20-methyl-8-iso-13-trans-prostenoate                                          ethyl 8β-methyl-9-oxo-15-hydroxy-7-nor-                                  20-methyl-13-cis-prostenoate                                                  ethyl 8α-methyl-9-oxo-15-hydroxy-7-nor-                                 20-methyl-8-iso-13-cis-prostenoate                  1200 70         1178      ethyl 8β-methyl-9-oxo-15-hydroxy-2-fluoro-                               N                                                                             17,17-dimethyl-13-trans-prostenoate                                           ethyl 8α-methyl-9-oxo-15-hydroxy-2-fluoro-                              O                                                                             17,17-dimethyl-8-iso-13-trans-prostenoate                                     ethyl 8β-methyl-9-oxo-15-hydroxy-2-fluoro-                               17,17-dimethyl-13-cis-prostenoate                                             ethyl 8α-methyl-9-oxo-15-hydroxy-2-fluoro-                              17,17-dimethyl-8-iso-13-cis-prostenoate             1201 111         728      ethyl 8β-methyl-9-oxo-15-hydroxy-10a-homo-                               13-trans-prostenoate                                                          ethyl 8α-methyl-9-oxo-15-hydroxy-10a-homo-                              8-iso-13-trans-prostenoate                                                    ethyl 8β-methyl-9-oxo-15-hydroxy-10a-homo-                               13-cis-prostenoate                                                            ethyl 8α-methyl-9-oxo-15-hydroxy-10a-homo-                              8-iso-13-cis-prostenoate                            1202 79         1186      ethyl 8β-methyl-9-oxo-15-hydroxy-2-phenyl-                               20-methyl-13-trans-prostenoate                                                ethyl 8α-methyl-9-oxo-15-hydroxy-2-phenyl-                              20-methyl-8-iso-13-trans-prostenoate                                          ethyl 8β-methyl-9-oxo-15-hydroxy-2-phenyl-                               A                                                                             20-methyl-13-cis-prostenoate                                                  ethyl 8α-methyl-9-oxo-15-hydroxy-2-phenyl-                              B                                                                             20-methyl-8-iso-13-cis-prostenoate                  1203 900        1182      methyl 8β-methyl-9-oxo-15-hydroxy-                                       5-cis,13-trans,17-cis-prostatrienoate                                         methyl 8α-methyl-9-oxo-15-hydroxy-8-iso-                                5-cis,13-trans,17-cis-prostatrienoate                                         methyl 8β-methyl-9-oxo-15-hydroxy-5-cis,                                 13-cis,17-cis-prostatrienoate                                                 methyl 8α-methyl-9-oxo-15-hydroxy-8-iso-                                5-cis,13-cis,17-cis-prostatrienoate                 1204 900         728      ethyl 8β-methyl-9-oxo-15-hydroxy-5-cis,                                  13-trans-prostadienoate                                                       ethyl 8α-methyl-9-oxo-15-hydroxy-8-iso-                                 5-cis,13-trans-prostadienoate                                                 ethyl 8β-methyl-9-oxo-15-hydroxy-5-cis,                                  13-cis-prostadienoate                                                         ethyl 8α-methyl-9-oxo-15-hydroxy-8-iso-                                 5-cis,13-cis-prostadienoate                         1205 900        1185      ethyl 8β-methyl-9-oxo-15-hydroxy-20-ethyl-                               S                                                                             5-cis,13-trans-prostadienoate                                                 ethyl 8α-methyl-9-oxo-15-hydroxy-20-ethyl-                              T                                                                             8-iso-5-cis,13-trans-prostadienoate                                           ethyl 8β-methyl-9-oxo-15-hydroxy-20-ethyl-                               5-cis,13-cis-prostadienoate                                                   ethyl 8α-methyl-9-oxo-15-hydroxy-20-ethyl-                              8-iso-5-cis,13-cis-prostadienoate                   __________________________________________________________________________

EXAMPLES 1206-1273

Treatment of the designated 9-oxo-prostenoic acid and ester derivativeslisted in Table 35 below with medium borohydride in ethanol as describedin Example 257 gives the product 9α and 9β hydroxy derivatives of thetable, which are seperable by standard chromatographic techniques.

                  TABLE 35                                                        ______________________________________                                        Ex-     Starting 9-oxo-                                                                             Product 9-hydroxy                                       ample   derivative    derivatives                                             ______________________________________                                        1206    11-deoxy-8β-                                                                           11-deoxy-8β-methyl-pros-                                   methyl-prosta-                                                                              taglandin F.sub.1 α and F.sub.1 β                    glandin E.sub.1 meth-                                                                       methyl esters                                                   yl ester                                                                      (Example 1188)                                                        1207    11-deoxy-8α-                                                                          11-deoxy-8α-methyl-8-iso-                                 methyl-8-iso- prostaglandin F.sub.1 α and                               prostaglandin F.sub.2 βmethyl esters                                     E.sub.1 methyl ester                                                          (Example 1188)                                                        1208    methyl 15-hy- methyl 9α/β, 15-di-                                  droxy-8β-meth-                                                                         hydroxy-8β-methyl-13-                                      yl-9-oxo-13-  cis-prostenoates                                                cis-prostenoate                                                               (Example 1188)                                                        1209    methyl 15-hy- methyl 9α/β,15-dihydroxy                             droxy-8α-meth-                                                                        8α-methyl-8-iso-13-cis-                                   yl-9-oxo-13-  prostenoates                                                    cis-prosteno-                                                                 ate (Example                                                                  1188)                                                                 1210    ethyl 8β-meth-                                                                         ethyl 8β-methyl-9α/β,15-                        yl-9-oxo-15-  dihydroxy-16,16-dimeth-                                         hydroxy-16-   yl-13-trans-prosteno-                                           16-dimethyl-  ates                                                            13-trans-                                                                     prostenoate                                                                   (Example 1190)                                                        1211    ethyl 8α-meth-                                                                        ethyl 8α-methyl-9α/β,15-                       yl-9-oxo-15-  dihydroxy-16,16-dimeth-                                         hydroxy-16,-  yl-8-iso-13-trans-pros-                                         16-dimethyl-  tenoates                                                        8-iso-13-                                                                     trans-prosten-                                                                oate (Example                                                                 1190)                                                                 1212    ethyl 8β-meth-                                                                         ethyl 8β-methyl-9α/β,15-                        yl-9-oxo-15-hy-                                                                             dihydroxy-16,16-dimeth-                                         droxy-16,16-  yl-13-cis-prostenoates                                          dimethyl-13-                                                                  cis-prosteno-                                                                 ate (Example                                                                  1190)                                                                 1213    ethyl 8α-meth-                                                                        ethyl 8α-methyl-9α/β,15-                       yl-9-oxo-15-  dihydroxy-16,16-dimeth-                                         hydroxy-16,-  yl-8-iso-13-cis-prosten-                                        16-dimethyl-8-                                                                              oates                                                           iso-13-cis-                                                                   prostenoate                                                                   (Example 1190)                                                                ethyl-                                                                1214    8β-methyl-9-                                                                           ethyl 8β-methyl-9α/β,15-                        oxo-15-hydrox-                                                                              dihydroxy-17,17-dimeth-                                         y-17,17-dimeth-                                                                             yl-13-trans-prostenoates                                        yl-13-trans-                                                                  prostenoate                                                                   (Example 1191)                                                        1215    ethyl 8α-meth-                                                                        ethyl 8α-methyl-9α/β,15-                       yl-9-oxo-15-  dihydroxy-17,17-dimeth-                                         hydroxy-17,17-                                                                              yl-8-iso-13-trans-pros-                                         dimethyl-8-   tenoates                                                        iso-13-trans-                                                                 prostenoate                                                                   (Example 1191)                                                        1216    ethyl 8β-meth-                                                                         ethyl 8β-methyl-9α/β,15-                        yl-9-oxo-15-  dihydroxy-17,17-dimeth-                                         hydroxy-17,17-                                                                              yl-13-cis-prostenoates                                          dimethyl-13-                                                                  cis-prosteno-                                                                 ate (Example                                                                  1191)                                                                 1217    ethyl 8α-meth-                                                                        ethyl 8α-methyl-9α/β,15-                       yl-9-oxo-15-hy-                                                                             dihydroxy-17,17-dimeth-                                         droxy-17,17-di                                                                              yl-8-iso-13-cis-prosten-                                        methyl-8-iso- oates                                                           13-cis-prosten-                                                               oate (Example                                                                 1191)                                                                 1218    ethyl 8β-meth-                                                                         ethyl 8β-methyl-9α/β,15-                        yl-9-oxo-15-hy-                                                                             dihydroxy-13-trans,17-                                          droxy-13-trans-                                                                             cis-prostadienoates                                             17-cis-prosta-                                                                dienoate (Exam-                                                               ple 1192)                                                             1219    ethyl 8α-meth-                                                                        ethyl 8α-methyl-9α/β,15-                       yl-9-oxo-15-hy-                                                                             dihydroxy-8-iso-13-trans                                        droxy-8-iso-13-                                                                             17-cis-prostadienoates                                          trans,17-cis-                                                                 prostadienoate                                                                (Example 1192)                                                        1220    ethyl 8β-meth-                                                                         ethyl 8β-methyl-9α/β,15-                        yl-9-oxo-15-hy-                                                                             dihydroxy-13-cis,17-                                            droxy-13-cis,-                                                                              cis-prostadienoates                                             17-cis-prostadi-                                                              enoate (Example                                                               1192)                                                                 1221    ethyl 8α-methyl-                                                                      ethyl 8α-methyl-9α/β,15-                       9-oxo-15-hy-  dihydroxy-8-iso-13-cis-                                         droxy-8-iso-13-                                                                             17-cis-prostadienoates                                          cis,17-cis-pros-                                                              tadienoate (Exam-                                                             ple 1192)                                                             1222    ethyl 8β-methyl-                                                                       ethyl 8β-methyl-9α/β,15-                        9-oxo-15-hy-  dihydroxy-20-ethyl-13-                                          droxy-20-ethyl-13-                                                                          trans-prostenoates                                              trans-prosteno-                                                               ate (Example 1193)                                                    1223    ethyl 8α -methyl-                                                                     ethyl 8α-methyl-9α/β,15-                       9-oxo-15-hy-  dihydroxy-20-ethyl-8-                                           droxy-20-ethyl-8-                                                                           iso-13-trans-prosteno-                                          iso-13-trans- ates                                                            prostenoate                                                                   (Example 1193)                                                        1224    ethyl 8β-methyl-                                                                       ethyl 8β-methyl-9α/β,15-                        9-oxo-15-hy-  dihydroxy-20-ethyl-13-                                          droxy-20-ethyl-13-                                                                          cis-prostenoates                                                cis-prostenoate                                                               (Example 1193)                                                        1225    ethyl 8α-methyl-                                                                      ethyl 8α-methyl-9α/β,15-                       9-oxo-15-hy-  dihydroxy-20-ethyl-8-                                           droxy-20-ethyl-                                                                             iso-13-cis-prostenoates                                         8-iso-13-cis-                                                                 prostenoate                                                                   (Example 1193)                                                        1226    decyl 8β-methyl-                                                                       decyl 8β-methyl-9α/β,15-                        9-oxo-15-hy-  dihydroxy-20-methyl-13-                                         droxy-20-methyl-                                                                            trans-prostenoates                                              13-trans-pros-                                                                tenoate (Example                                                              1194)                                                                 1127    decyl 8α-methyl-                                                                      decyl 8α-methyl-9α/β,15-                       9-oxo-15-hy-  dihydroxy-20-methyl-8-                                          droxy-20-methyl-                                                                            iso-13-trans-prosteno-                                          8-iso-13-trans-                                                                             ates                                                            prostenoate                                                                   (Example 1194)                                                        1128    decyl 8β-methyl-                                                                       decyl 8β-methyl-9α/β,15-                        9-oxo-15-hy-  dihydroxy-20-methyl-13-                                         droxy-20-methyl-                                                                            cis-prostenoates                                                13-cis-prosten-                                                               oate (Example                                                                 1194)                                                                 1229    ethyl 8α-methyl-                                                                      ethyl 8α-methyl-9α/β,15-                       9-oxo-15-hy-  dihydroxy-20-methyl-8-                                          droxy-20-methyl-                                                                            iso-13-cis-prostenoates                                         8-iso-13-cis-                                                                 prostenoate                                                                   (Example 1194)                                                        1230    ethyl 8β-methyl-                                                                       ethyl 8β-methyl-9α/β,15-                        9-oxo-15-hy-  dihydroxy-7a,7b-bis-                                            droxy-7a,7b-bis-                                                                            homo-13-trans-prosteno-                                         homo-13-trans-                                                                              ates                                                            prostenoate                                                                   (Example 1195)                                                        1231    ethyl 8α-methyl-                                                                      ethyl 8α-methyl-9α/β,15-                       9-oxo-15-hy-  dihydroxy-7a,7b-bis-                                            droxy-7a,7b-bis-                                                                            homo-8-iso-13-trans-                                            homo-8-iso-13-                                                                              prostenoates                                                    trans-prosteno-                                                               ate (Example                                                                  1195)                                                                 1232    ethyl 8β-methyl-                                                                       ethyl 8β-methyl-9α/β,15-                        9-oxo-15-hy-  dihydroxy-7a,7b-bis-                                            droxy-7a,7b-bis-                                                                            homo-13-cis-prosteno-                                           homo-13-cis-pros-                                                                           ates                                                            tenoate (Example                                                              1195)                                                                 1233    ethyl 8α-methyl-                                                                      ethyl 8α-methyl-9α/β,15-                       9-oxo-15-hy-  dihydroxy-7a,7b-bis-                                            droxy-7a,7b-bis-                                                                            homo-8-iso-13-cis-pros-                                         homo-8-iso-13-                                                                              tenoates                                                        cis-prostenoate                                                               (Example 1195)                                                        1234    ethyl 8β-methyl-                                                                       ethyl 8β-methyl-9α/β,15-                        9-oxo-15-hy-  dihydroxy-2,20-bis-                                             droxy-2,20-bis-                                                                             ethyl-13-trans-prosteno-                                        ethyl-13-trans-                                                                             ates                                                            prostenoate                                                                   (Example 1196)                                                        1235    ethyl 8α-methyl-                                                                      ethyl 8α-methyl-9α/β,15-                       9-oxo-15-hy-  dihydroxy-2,20-bis-                                             droxy-2,20-bis-                                                                             ethyl-8-iso-13-trans-                                           ethyl-8-iso-13-                                                                             prostenoates                                                    trans-prosteno-                                                               ate (Example                                                                  1196)                                                                 1236    ethyl 8β-methyl-                                                                       ethyl 8β-methyl-9α/β,15-                        9-oxo-15-hy-  dihydroxy-2,20-bis-                                             droxy-2,20-bis-                                                                             ethyl-13-cis-prosteno-                                          ethyl-13-cis- ates                                                            prostenoate                                                                   (Example 1196)                                                        1237    ethyl 8α-methyl-                                                                      ethyl 8α-methyl-9α/β,15-                       9-oxo-15-hy-  dihydroxy-2,20-bis-                                             droxy-2,20-bis-                                                                             ethyl-8-iso-13-cis-pros-                                        ethyl-8-iso-13-                                                                             tenoates                                                        cis-prostenoate                                                               (Example 1196)                                                        1238    ethyl 8β-methyl-                                                                       ethyl 8β-methyl-9α/β,15-                        9-oxo-15-hy-  dihydroxy-3-oxa-16,16-                                          droxy-3-oxa-16,-                                                                            dimethyl-13-trans-pros-                                         16-dimethyl-13-                                                                             tenoates                                                        trans-prosteno-                                                               ate (Example                                                                  1197)                                                                 1239    ethyl 8α-methyl-                                                                      ethyl 8α-methyl-9α/β,15-                       9-oxo-15-hy-  dihydroxy-3-oxa-16,16-                                          droxy-3-oxa-16,-                                                                            dimethyl-8-iso-13-trans-                                        16-dimethyl-8-                                                                              prostenoates                                                    iso-13-trans-                                                                 prostenoate                                                                   (Example 1197)                                                                              1197)                                                   1240    ethyl 8β-methyl-                                                                       ethyl 8β-methyl-9α/β,15-                        9-oxo-15-hy-  dihydroxy-3-oxa-16,16-                                          droxy-3-oxa-16,-                                                                            dimethyl-13-cis-pros-                                           16-dimethyl-13-                                                                             tenoates                                                        cis-prostenoate                                                               (Example 1197)                                                        1241    ethyl 8α-methyl-                                                                      ethyl 8α-methyl-9α/β,15-                       9-oxo-15-hy-  dihydroxy-3-oxa-16,16-                                          droxy-3-oxa-16,-                                                                            dimethyl-8-iso-13-cis-                                          16-dimethyl-8-                                                                              prostenoates                                                    iso-13-cis-                                                                   prostenoate                                                                   (Example 1197)                                                        1242    ethyl 8β-methyl-                                                                       ethyl 8β-methyl-9α/β,15-                        9-oxo-15-hy-  dihydroxy-3-oxa-13-                                             droxy-3-oxa-13-                                                                             trans,17-cis-prostadi-                                          trans,17-cis- enoates                                                         prostadienoate                                                                (Example 1198)                                                        1243    ethyl 8α-methyl-                                                                      ethyl 8α-methyl-9α/β,15-                       9-oxo-15-hy-  dihydroxy-3-oxa-8-iso-                                          droxy-3-oxa-8-                                                                              13-trans,17-cis-prosta-                                         iso-13-trans,-                                                                              dienoates                                                       17-cis-prostadi-                                                              enoate (Example                                                               1198)                                                                 1244    ethyl 8β-methyl-                                                                       ethyl 8β-methyl-9α/β,15-                        9-oxo-15-hy-  dihydroxy-3-oxa-13-cis-                                         droxy-3-oxa-13-                                                                             17-cis-prostadienoates                                          cis,17-cis-pros-                                                              tadienoate (Exam-                                                             ple 1198)                                                             1245    ethyl 8α-methyl-                                                                      ethyl 8α-methyl-9α/β,15-                       9-oxo-15-hy-  dihydroxy-3-oxa-8-iso-                                          droxy-3-oxa-8-iso                                                                           13-cis,17-cis-prosta-                                           13-cis,17-cis-                                                                              dienoates                                                       prostadienoate                                                                (Example 1198)                                                        1246    ethyl 8β-methyl-                                                                       ethyl 8β-methyl-9α/β,15-                        9-oxo-15-hy-  dihydroxy-7-nor-20-                                             droxy-7-nor-20-                                                                             methyl-13-trans-pros-                                           methyl-13-trans-                                                                            tenoates                                                        prostenoate                                                                   (Example 1199)                                                        1247    ethyl 8α-methyl-                                                                      ethyl 8α-methyl-9α/β,15-                       9-oxo-15-hy-  dihydroxy-7-nor-20-                                             droxy-7-nor-20-                                                                             methyl-8-iso-13-trans-                                          methyl-8-iso-13-                                                                            prostenoates                                                    trans-prosteno-                                                               ate (Example 1199)                                                    1248    ethyl 8β-methyl-                                                                       ethyl 8β-methyl-9α/β,15-                        9-oxo-15-hy-  dihydroxy-7-nor-20-                                             droxy-7-nor-20-                                                                             methyl-13-cis-prosteno-                                         methyl-13-cis-                                                                              ates                                                            prostenoate                                                                   (Example 1199)                                                        1249    ethyl 8α-methyl-                                                                      ethyl 8α-methyl-9α/β,15-                       9-oxo-15-hy-  dihydroxy-7-nor-20-                                             droxy-7-nor-20-                                                                             methyl-8-iso-13-cis-                                            methyl-8-iso- prostenoates                                                    13-cis-prosteno-                                                              ate (Example                                                                  1199)                                                                 1250    ethyl 8β-methyl-                                                                       ethyl 8β-methyl-9α/β,15-                        9-oxo-15-hy-  dihydroxy-2-fluoro-17,-                                         droxy-2-fluoro-                                                                             17-dimethyl-13-trans-                                           17,17-dimethyl-                                                                             prostenoates                                                    13-trans-prosten-                                                             oate (Example                                                                 1200)                                                                 1251    ethyl 8α-methyl-                                                                      ethyl 8α-methyl-9α/β,15-                       9-oxo-15-hy-  dihydroxy-2-fluoro-17,-                                         droxy-2-fluoro-                                                                             17-dimethyl-8-iso-13-                                           17,17-dimethyl-                                                                             trans-prostenoates                                              8-iso-13-trans-                                                               prostenoate                                                                   (Example 1200)                                                        1252    ethyl 8β-methyl-                                                                       ethyl 8β-methyl-9α/β,15-                        9-oxo-15-hy-  dihydroxy-2-fluoro-17,-                                         droxy-2-fluoro-17                                                                           17-dimethyl-13-cis-pros-                                        17-dimethyl-13-                                                                             tenoates                                                        cis-prostenoate                                                               (Example 1200)                                                        1253    ethyl 8α-methyl-                                                                      ethyl 8α-methyl-9α/β,15-                       9-oxo-15-hy-  dihydroxy-2-fluoro-17,-                                         droxy-2-fluoro-                                                                             17-dimethyl-8-iso-13-                                           17,17-dimethyl-                                                                             cis-prostenoates                                                8-iso-13-cis-                                                                 prostenoate                                                                   (Example 1200)                                                        1254    ethyl 8β-methyl-                                                                       ethyl 8β-methyl-9α/β,15-                        9-oxo-15-hy-  dihydroxy-10a-homo-13-                                          droxy-10a-homo-13-                                                                          trans-prostenoates                                              trans-prosteno-                                                               ate (Example                                                                  1201)                                                                 1255    ethyl 8α-methyl-                                                                      ethyl 8α-methyl-9α/β,15-                       9-oxo-15-hy-  dihydroxy-10a-homo-8-                                           droxy-10a-homo-8-                                                                           iso-13-trans-prosteno-                                          iso-13-trans- ates                                                            prostenoate                                                                   (Example 1201)                                                        1256    ethyl 8β-methyl-                                                                       ethyl 8β-methyl-9α/β,15-                        9-oxo-15-hy-  dihydroxy-10a-homo-13-                                          droxy-10a-homo-                                                                             cis-prostenoates                                                13-cis-prosten-                                                               oate (Example                                                                 1201)                                                                 1257    ethyl 8α-methyl-                                                                      ethyl 8α-methyl-9α/β,15-                       9-oxo-15-hy-  dihydroxy-10a-homo-8-                                           droxy-10a-homo-8-                                                                           iso-13-cis-prostenoates                                         iso-13-cis-pros-                                                              tenoate (Example                                                              1201)                                                                 1258    ethyl 8β-methyl-                                                                       ethyl 8β-methyl-9α/β,15-                        9-oxo-15-hy-  dihydroxy-2-phenyl-20-                                          droxy-2-phenyl-                                                                             methyl-13-trans-prosten-                                        20-methyl-13- oates                                                           trans-prosteno-                                                               ate (Example                                                                  1202)                                                                 1259    ethyl 8α-methyl-                                                                      ethyl 8α-methyl-9α/β,15-                       9-oxo-15-hy-  dihydroxy-2-phenyl-20-                                          droxy-2-phenyl-                                                                             methyl-8-iso-13-trans-                                          20-methyl-8-iso-                                                                            prostenoates                                                    13-trans-pros-                                                                tenoate (Example                                                              1202)                                                                 1260    ethyl 8β-methyl-                                                                       ethyl 8β-methyl-9α/β,15-                        9-oxo-15-hy-  dihydroxy-2-phenyl-20-                                          droxy-2-phenyl-                                                                             methyl-13-cis-prosteno-                                         20-methyl-13-cis-                                                                           ates                                                            prostenoate                                                                   (Example 1202)                                                        1261    ethyl 8α-methyl-                                                                      ethyl 8α-methyl-9α/β,15-                       9-oxo-15-hy-  dihydroxy-2-phenyl-20-                                          droxy-2-phenyl-                                                                             methyl-8-iso-13-cis-                                            20-methyl-8-iso-                                                                            prostenoates                                                    13-cis-prosteno-                                                              ates (Example                                                                 1202)                                                                 1262    methyl 8β-methyl-                                                                      methyl 8β-methyl-9α/β,15-                       9-oxo-15-hy-  dihydroxy-5-cis,13-                                             droxy-5-cis,13-                                                                             trans,17-cis-prostatri-                                         trans,17-cis-pros-                                                                          enoates                                                         tatrienoate                                                                   (Example 1203)                                                        1263    methyl 8α-methyl-                                                                     methyl 8α-methyl-9α/β,15-                      9-oxo-15-hy-  dihydroxy-8-iso-5-cis,-                                         droxy-8-iso-5-                                                                              13-trans,17-cis-prosta-                                         cis,13-trans,17-                                                                            trienoates                                                      cis-prostatri-                                                                enoate                                                                        (Example 1203)                                                        1264    methyl 8β-methyl-                                                                      methyl 8β-methyl-9α/β,-                         9-oxo-15-hy-  15-dihydroxy-5-cis,13-                                          droxy-5-cis,13-                                                                             cis,17-cis-prostatri-                                           cis,17-cis-pros-                                                                            enoates                                                         tatrienoate                                                                   (Example 1203)                                                        1265    methyl 8α-methyl-                                                                     methyl 8α-methyl-9α/β,15-                      9-oxo-15-hy-  dihydroxy-8-iso-5-cis,-                                         droxy-8-iso-5-                                                                              13-cis,17-cis-prostatri-                                        cis,13-cis,17-                                                                              enoates                                                         cis-prostatrien-                                                              oate (Example                                                                 1203)                                                                 1266    ethyl 8β-methyl-                                                                       ethyl 8β-methyl-9α/β,-                          9-oxo-15-hy-  15-dihydroxy-5-cis,13-                                          droxy-5-cis,13-                                                                             trans-prostadienoates                                           trans-prostadi-                                                               enoate (Example                                                               1204)                                                                 1267    ethyl 8α-methyl-                                                                      ethyl 8α-methyl-9α/β,-                         9-oxo-15-hy-  15-dihydroxy-8-iso-5-                                           droxy-8-iso-5-                                                                              cis,13-trans-prosta-                                            cis,13-trans- dienoates                                                       prostadienoate                                                                (Example 1204)                                                        1268    ethyl 8β-methyl-                                                                       ethyl 8β-methyl-9α/β,-                          9-oxo-15-hy-  15-dihydroxy-5-cis,13-                                          droxy-5-cis,13-                                                                             cis-prostadienoates                                             cis-prostadien-                                                               oate (Example                                                                 1204)                                                                 1269    ethyl 8α-methyl-                                                                      ethyl 8α-methyl-9α/β,-                         9-oxo-15-hy-  15-dihydroxy-8-iso-5-                                           droxy-8-iso-5-                                                                              cis,13-cis-prostadien-                                          cis,13-cis-   oates                                                           prostadienoate                                                                (Example 1204)                                                        1270    ethyl 8β-methyl-                                                                       ethyl 8β-methyl-9α/β,-                          9-oxo-15-hy-  15-dihydroxy-20-ethyl-                                          droxy-20-ethyl-                                                                             5-cis,13-trans-prosta-                                          5-cis,13-trans-                                                                             dienoates                                                       prostadienoate                                                                (Example 1205)                                                        1271    ethyl 8α-methyl-                                                                      ethyl 8α-methyl-9α/β,-                         9-oxo-15-hy-  15-dihydroxy-20-ethyl-                                          droxy-20-ethyl-8-                                                                           8-iso-5-cis,13-trans-                                           iso-5-cis,13- prostadienoates                                                 trans-prostadien                                                              oate (Example                                                                 1205)                                                                 1272    ethyl 8β-methyl-                                                                       ethyl 8β-methyl-9α/β,-                          9-oxo-13-hy-  15-dihydroxy-20-ethyl-                                          droxy-20-ethyl-                                                                             5-cis,13-cis-prostadi-                                          5-cis,13-cis- enoates                                                         prostadienoate                                                                (Example 1205)                                                        1273    ethyl 8α-methyl-                                                                      ethyl 8α-methyl-9α/β,-                         9-oxo-15-hy-  15-dihydroxy-20-ethyl-                                          droxy-20-ethyl-                                                                             8-iso-5-cis,13-cis-                                             8-iso-5-cis,13-                                                                             prostadienoates                                                 cis-prostadien-                                                               oate (Example                                                                 1205)                                                                 ______________________________________                                    

EXAMPLES 1274-1299

In the manner of Example 93, the various cyclopentenones of Table 36,which follows, are converted to the corresponding 4-bromo derivatives.

                  TABLE 36                                                        ______________________________________                                                Starting                                                              Ex-     Cyclopentenone Product 4-Bromocyclo-                                  ample   of Example     pentenones                                             ______________________________________                                        1274    13             4-bromo-2-(6-carbeth-                                                         oxyhexyl)-cyclopent-2-                                                        en-1-one                                               1275    83             4-bromo-2-(6-carbo-                                                           methoxyhexyl)cyclopent-                                                       2-en-1-one                                             1276    15             4-bromo-2-(4-carbeth-                                                         oxybutyl)cyclopent-2-en-                                                      1-one                                                  1277    14             4-bromo-2-(3-carbethoxy-                                                      propyl)cyclopent-2-en-1-                                                      one                                                    1278     2             4-bromo-2-(4-carboxy-                                                         butyl)cyclopent-2-en-                                                         1-one                                                  1279     5             4-bromo-2-(3-carboxy-                                                         propyl)cyclopent-2-en-1-                                                      one                                                    1280    22             4-bromo-2-(8-carboxy-                                                         octyl)cyclopent-2-en-1-                                                       one                                                    1281    23             4-bromo-2-(8-carbethoxy-                                                      octyl)cyclopent-2-en-1-                                                       one                                                    1282    30             4-bromo-2-(6-carboxy-                                                         octyl)cyclopent-2-en-1-                                                       one                                                    1283    31             4-bromo-2-(6-carbethoxy-                                                      octyl)cyclopent-2-en-1-                                                       one                                                    1284    92             4-bromo-2-(6-carboxy-                                                         5,5-dimethylhexyl)cyclo-                                                      pent-2-en-1-one                                        1285    41             4-bromo-2-(6-carbethoxy-                                                      5,5-dimethylhexyl)cyclo-                                                      pent-2-en-1-one                                        1286    45             4-bromo-2-(6-carboxy-5-                                                       oxahexyl)cyclopent-2-                                                         en-1-one                                               1287    46             4-bromo-2-(6-carbethoxy-                                                      5-oxahexyl)cyclopent-2-                                                       en-1-one                                               1288    69             4-bromo-2-(6-carboxy-6-                                                       fluorohexyl)cyclopent-                                                        2-en-1-one                                             1289    70             4-bromo-2-(6-carbethoxy-                                                      6-fluorohexyl)cyclopent-                                                      2-en-1-one                                             1290    52             4-bromo-2-(5-carboxy-                                                         pentyl)cyclopent-2-en-1-                                                      one                                                    1291    53             4-bromo-2-(5-carbethoxy-                                                      pentyl)cyclopent-2-en-                                                        1-one                                                  1292    73             4-bromo-2-(7-carboxy-                                                         heptyl)cyclopent-2-en-1-                                                      one                                                    1293    74             4-bromo-2-(7-carbethoxy-                                                      heptyl)cyclopent-2-en-1-                                                      one                                                    1294    78             4-bromo-2-(6-carboxy-6-                                                       phenylhexyl)cyclopent-2-                                                      en-1-one                                               1295    79             4-bromo-2-(6-carbethoxy-                                                      6-phenylhexyl)cyclopent-                                                      2-en-1-one                                             1296    81             4-bromo-2-(6-carbo-n-                                                         butoxyhexyl)cyclopent-                                                        2-en-1-one                                             1297    82             4-bromo-2-(6-carbo-iso-                                                       propoxyhexyl)-cyclo-                                                          pent-2-en-1-one                                        1298    84             4-bromo-2-(6-carbo-n-                                                         decyloxyhexyl)cyclopent-                                                      2-en-1-one                                             1299    98             4-bromo-2-(6-carboxy-                                                         heptyl)-cyclopent-2-en-                                                       1-one                                                  ______________________________________                                    

EXAMPLE 1300 Preparation of4-hydroxy-2-(8-carboxyoctyl)cyclopent-2-en-1-one

To a stirred solution of 57.2 g. of crude4-bromo-2-(8-carboxyoctyl)cyclopent-2-en-1-one (Example 1280) in 500 ml.of acetone and 325 ml. of water at 3° C. is added 44.1 g. (0.226 moles)of silver fluoborate during a 15 minute period. The mixture is stirredat 0°-3° C. for 2 hours and filtered. The filtrate is diluted withwater, saturated with solid sodium chloride, and extracted with ether.The extract is washed with saturated sodium chloride solution, driedover magnesium sulfate, and concentrated. Partition chromatography ofthe residue on Gelite gives white crystals, m.p. 58°-66° C.,λ_(max).^(MeOH) =223 mμ (7800); νmax (KBr)=3340 (hydroxyl groups), 1705(carbonyl groups), and 1625 cm⁻¹ (olefin group).

EXAMPLE 1301 Preparation of4-acetoxy-2-(6-carbethoxyhexyl)cyclopent-2-en-1-one

A mixture of 51.6 g. (0.137 moles) of crude4-bromo-2-(6-carbethoxyhexyl)cyclopent-2-en-1-one (Example 1274), 27 g.(0.162 moles) of silver acetate, and 200 ml. of glacial acetic acid isstirred at reflux for 4.5 hours. The mixture is cooled, and solids areremoved by filtration. The filtrate is concentrated and extracted withhot hexane. The extract is washed with saturated sodium bicarbonatesolution and saturated sodium chloride solution, dried over magnesiumsulfate, and concentrated to give an oil. The crude product is distilledat reduced pressure to give a liquid, b.p. 152°-163° C. (0.01 mm);λ_(max).^(MeOH) =223 mμ (10700); νmax.=1745 (ester carbonyl groups),1725 (ketone carbonyl groups), and 1235 cm⁻¹ (acetoxy group).

EXAMPLES 1302-1326

By the procedure of Example 94 the various 4-bromocyclopentenones of thefollowing Table 37 are solvolyzed in acetone-water in the presence ofsilver fluoborate to provide the product 4-hydroxycyclopentenones of theTable.

                  TABLE 37                                                        ______________________________________                                                Starting 4-bromo                                                                              Product                                               Ex-     cyclopentenones 4-Hydroxycyclopent-2-                                 ample   of Example      en-1-ones                                             ______________________________________                                        1302    1274            4-hydroxy-2-(6-carb-                                                          ethoxyhexyl)cyclopent-                                                        2-en-1-one                                            1303    1275            4-hydroxy-2-(6-carbo-                                                         methoxyhexyl)cyclopent-                                                       2-en-1-one                                            1304    1276            4-hydroxy-2-(4-carb-                                                          ethoxybutyl)cyclopent-                                                        2-en-1-one                                            1305    1277            4-hydroxy-2-(3-carb-                                                          ethoxypropyl)cyclopent-                                                       2-en-1-one                                            1306    1278            4-hydroxy-2-(4-carboxy-                                                       butyl)cyclopent-2-en-                                                         1-one                                                 1307    1279            4-hydroxy-2-(3-carboxy-                                                       propyl)cyclopent-2-en-                                                        1-one                                                 1308    1281            4-hydroxy-2-(8-carb-                                                          ethoxyoctyl)cyclopent-                                                        2-en-1-one                                            1309    1282            4-hydroxy-2-(6-carboxy-                                                       octyl)cyclopent-2-en-                                                         1-one                                                 1310    1283            4-hydroxy-2-(6-carb-                                                          ethoxyoctyl)cyclopent-                                                        2-en-1-one                                            1311    1284            4-hydroxy-2-(6-carboxy-                                                       5,5-dimethylhexyl)-                                                           cyclopent-2-en-1-one                                  1312    1285            4-hydroxy-2-(6-carb-                                                          ethoxy-5,5-dimethyl-                                                          hexyl)cyclopent-2-en-                                                         1-one                                                 1313    1286            4-hydroxy-2-(6-carboxy-                                                       5-oxahexyl)cyclopent-                                                         2-en-1-one                                            1314    1287            4-hydroxy-2-(6-carb-                                                          ethoxy-5-oxahexyl)-                                                           cyclopent-2-en-1-one                                  1315    1288            4-hydroxy-2-(6-carboxy-                                                       6-fluorohexyl)cyclo-                                                          pent-2-en-1-one                                       1316    1289            4-hydroxy-2-(6-carb-                                                          ethoxy-6-fluorohexyl)-                                                        cyclopent-2-en-1-one                                  1317    1290            4-hydroxy-2-(5-carboxy-                                                       pentyl)cyclopent-2-en-                                                        1-one                                                 1318    1291            4-hydroxy-2-(5-carb-                                                          ethoxypentyl)cyclo-                                                           pent-2-en-1-one                                       1319    1292            4-hydroxy-2-(7-carboxy-                                                       heptyl)cyclopent-2-en-                                                        1-one                                                 1320    1293            4-hydroxy-2-(7-carb-                                                          ethoxyheptyl)cyclopent-                                                       2-en-1-one                                            1321    1294            4-hydroxy-2-(6-carboxy-                                                       6-phenylhexyl)cyclo-                                                          pent-2-en-1-one                                       1322    1295            4-hydroxy-2-(6-carb-                                                          ethoxy-6-phenylhexyl)-                                                        cyclopent-2-en-1-one                                  1323    1296            4-hydroxy-2-(6-carbo-                                                         n-butoxyhexyl)cyclo-                                                          pent-2-en-1-one                                       1324    1297            4-hydroxy-2-(6-carbo-                                                         isopropoxyhexyl)cyclo-                                                        pent-2-en-1-one                                       1325    1298            4-hydroxy-2-(6-carbo-                                                         n-decyloxyhexyl)cyclo-                                                        pent-2-en-1-one                                       1326    1299            4-hydroxy-2-(6-carboxy-                                                       heptyl)cyclopent-2-en-                                                        1-one                                                 ______________________________________                                    

EXAMPLES 1327-1337

By the procedure of Example 95, the various 4-hydroxycyclopentenones ofTable 38, which follows, are converted to the tetrahydropyranyl4-tetrahydropyranyloxycyclopentenone esters of the table.

                  TABLE 38                                                        ______________________________________                                                               Product Tetrahydropyran-                                       Starting 4-hy- 2'-yl 4-tetrahydropy-                                  Ex-     droxycyclopenten-                                                                            ran-2'-yl-oxycyclopent-                                ample   one of Example 2-en-1-ones                                            ______________________________________                                        1327    1306           4-tetrahydropyran-2'-                                                         yloxy-2-(4-carbotetra-                                                        hydropyran-2'-yloxy-                                                          butyl)cyclopent-2-en-1-                                                       one                                                    1328    1307           4-tetrahydropyran-2'-                                                         yloxy-2-(3-carbotetra-                                                        hydropyran-2'-yloxy-                                                          propyl)cyclopent-2-en-                                                        1-one                                                  1329    1300           4-tetrahydropyran-2'-                                                         yloxy-2-(8-carbotetra-                                                        hydropyran-2'-yloxy-                                                          octyl)cyclopent-2-en-1-                                                       one                                                    1330    1309           4-tetrahydropyran-2'-                                                         yloxy-2-(6-carbotetra-                                                        hydropyran-2'-yloxy-                                                          octyl)cyclopent-2-en-1-                                                       one                                                    1331    1311           4-tetrahydropyran-2'-                                                         yloxy-2-(6-carbotetra-                                                        hydropyran-2'-yloxy-                                                          5,5-dimethylhexyl)-                                                           cyclopent-2-en-1-one                                   1332    1313           4-tetrahydropyran-2'-                                                         yloxy-2-(6-carbotetra-                                                        hydropyran-2'-yloxy-5-                                                        oxahexyl)cyclopent-2-                                                         en-1-one                                               1333    1315           4-tetrahydropyran-2'-                                                         yloxy-2-(6-carbotetra-                                                        hydropyran-2'-yloxy-6-                                                        fluorohexyl)cyclopent-                                                        2-en-1-one                                             1334    1317           4-tetrahydropyran-2'-                                                         yloxy-2-(5-carbotetra-                                                        hydropyran-2'-yloxy-                                                          pentyl)cyclopent-2-en-1-                                                      one                                                    1335    1319           4-tetrahydropyran-2'-                                                         yloxy-2-(7-carbotetra-                                                        hydropyran-2'-yloxyhep-                                                       tyl)cyclopent-2-en-1-                                                         one                                                    1336    1321           4-tetrahydropyran-2'-                                                         yloxy-2-(6-carbotetra-                                                        hydropyran-2'-yloxy-6-                                                        phenylhexyl)cyclopent-                                                        2-en-1-one                                             1337    1326           4-tetrahydropyran-2'-                                                         yloxy-2-(6-carbotetra-                                                        hydropyran-2'-yloxy-                                                          heptyl)cyclopent-2-en-                                                        1-one                                                  ______________________________________                                    

EXAMPLE 1338 Preparation of4-tetrahydropyranyloxy-2-(6-carbethoxyhexyl)cyclopent-2-en-1-one

To a stirred solution of 674 mg. (2.64 mmoles) of4-hydroxy-2-(6-carbethoxyhexyl)cyclopent-2-en-1-one (Example 1302) and2.22 g. (26.4 mmoles) of dihydropyran in 2.6 ml. of methylene chlorideis added 5.0 mg. (0.026 mmoles) of p-toluenesulfonic acid monohydrate.After stirring for 20 minutes at room temperature the solution isdiluted with ether and poured into saturated sodium chloride solutioncontaining a little sodium bicarbonate. The organic phase is separatedand washed with saturated sodium chloride solution. The extract is driedover magnesium sulfate, and volatile matter is evaporated at reducedpressure to give an oil, λ_(max).^(MeOH) =224 mμ (7950); max.=1735(ester carbonyl group), 1710 (ketone carbonyl group), and 1030 cm⁻¹(tetrahydropyranyloxy group).

EXAMPLE 1339-1352

In the manner of Example 1338 the alkyl 4-hydroxycyclopentenone estersof Table 39, which follows, are converted to the corresponding4-tetrahydropyranyloxy alkyl esters of the table.

                  TABLE 39                                                        ______________________________________                                                Starting 4-                                                                   hydroxycyclo- 4-tetrahydropyran-                                      Ex-     pentenone Esters                                                                            2'yloxycyclopent-                                       ample   of Example    2-en-1-one esters                                       ______________________________________                                        1339    1303          4-tetrahydropyran-2'-                                                         yloxy-2-(6-carbomethoxy-                                                      hexyl)cyclopent-2-en-1-                                                       one                                                     1340    1304          4-tetrahydropyran-2'-                                                         yloxy-2-(4-carbethoxy-                                                        butyl)cyclopent-2-en-1-                                                       one                                                     1341    1305          4-tetrahydropyran-2'-                                                         yloxy-2-(3-carbethoxy-                                                        propyl)cyclopent-2-en-1-                                                      one                                                     1342    1308          4-tetrahydropyran-2'-                                                         yloxy-2-(8-carbethoxy-                                                        octyl)cyclopent-2-en-1-                                                       one                                                     1343    1310          4-tetrahydropyran-2'-                                                         yloxy-2-(6-carbethoxy-                                                        octyl)cyclopent-2-en-1-                                                       one                                                     1344    1312          4-tetrahydropyran-2'-                                                         yloxy-2-(6-carbethoxy-5,                                                      5-dimethylhexyl)cyclo-                                                        pent-2-en-1-one                                         1345    1314          4-tetrahydropyran-2'-                                                         yloxy-2-(6-carbethoxy-5-                                                      oxahexyl)cyclopent-2-en-                                                      1-one                                                   1346    1316          4-tetrahydropyran-2'-                                                         yloxy-2-(6-carbethoxy-6-                                                      fluorohexyl)cyclopent-                                                        2-en-1-one                                              1347    1318          4-tetrahydropyran-2'-                                                         yloxy-2-(5-carbethoxy-                                                        pentyl)cyclopent-2-en-                                                        1-one                                                   1348    1320          4-tetrahydropyran-2'-                                                         yloxy-2-(7-carbethoxy-                                                        heptyl)cyclopent-2-en-1-                                                      one                                                     1349    1322          4-tetrahydropyran-2'-                                                         yloxy-2-(6-carbethoxy-6-                                                      phenylhexyl)cyclopent-2-                                                      en-1-one                                                1350    1323          4-tetrahydropyran-2'-                                                         yloxy-2-(6-carbo-n-                                                           butoxyhexyl)cyclopent-2-                                                      en-1-one                                                1351    1324          4-tetrahydropyran-2'-                                                         yloxy-2-(6-carbo-iso-                                                         propoxyhexyl)cyclopent-                                                       2-en-1-one                                              1352    1325          4-tetrahydropyran-2'-                                                         yloxy-2-(6-carbo-n-dec-                                                       yloxyhexyl)cyclopent-2-                                                       en-1-one                                                ______________________________________                                    

EXAMPLE 1353 Preparation of 8β-methyl-prostaglandin E₁,8α-methyl-8-iso-prostaglandin E₁,8β-methyl-9-oxo-11α,15-dihydroxy-13-cis-prostenoic acid, and8α-methyl-9-oxo-11α,15-dihydroxy-8-iso-13-cis-prostenoic acid

The Grignard reagent, prepared as described in Example 1187 from 1.54 g.of magnesium, 22.5 g. of 1-bromo-3-triphenylmethoxy-trans-1-octene(Example 728), and 30 ml. of tetrahydrofuran, is added to an ice cooledsolution of 17.75 g. of11-tetrahydropyranyloxy-2-(6-carbotetrahydropyranyloxyhexyl)-2-cyclopentenone(Example 95) and 1.25 g. of copper (I) iodide-tri-n-butylphosphinecomplex in 30 ml. of tetrahydrofuran over 15 minutes under an inertatmosphere. The mixture is stirred with cooling for 0.5 hour. To themixture is then added 100 g. of methyl iodide, the cooling bath is thenremoved and the mixture is stirred at ambient temperatures for 48 hours.The mixture is then poured into ice cold saturated ammonium chloridesolution and the layers are separated. The aqueous phase is washed withether and combined organic phase and washings are washed with saturatedbrine, and evaporated in vacuo. The residue is heated to 45° C. for 5hours with 840 ml. of 4:2:1 tetrahydrofuran-acetic acid-water under aninert atmosphere and is then evaporated to dryness in vacuo. The residueis chromatographed upon Silic AR CC-4® using a benzene-ethyl acetategradient as eluent to yield the title compounds as a mixture of8β-methyl-prostaglandin E₁ and 8α-methyl-8-iso-prostaglandin E₁ and amixture of 8β-methyl-9-oxo-11α,15-dihydroxy-13-cis-prostenoic acid and8α-methyl-9-oxo-11α,15-dihydroxy 8-iso-cis-8α isomers; resolution of themixtures is then accomplished by a combination of partitionchromatography and thin-layer chromatography.

EXAMPLES 1354-1386

Treatment of the blocked 4-oxycyclopent-2-en-1-ones listed in Table 40below by the procedure described in Example 1353 with the Grignardreagents, prepared by the procedure described in Example 1187 from thelisted 1-bromo-3-triphenylmethoxy-1-trans-alkenes, and then with methyliodide furnishes the product 8α- and 8β-methyl prostenoates of thetable. The products of Examples 1354-1378 inclusive are initiallyobtained as the corresponding15-O-triphenylmethyl-11-O-tetrahydropyranyl tetrahydropyranyl esters.These blocking groups are then cleaved by the procedure described inExample 1353 by treatment at 45° C. for five hours with 4:2:1tetrahydrofuran:acetic acid:water. The alkyl esters products of Examles1379-1385 inclusive are obtained initially as the corresponding15-O-triphenylmethyl-11-O-tetrahydropyranyl derivatives. These 11- and15-hydroxy blocking groups are then cleaved by the deblocking proceduredescribed in Example 1353. The products of Example 1386 are initiallyobtained as the corresponding 15-O-triphenylmethyl derivatives, whichare cleaved hydrolytically to the listed free 15 -ols by the processdescribed in Example 1353.

                                      TABLE 40                                    __________________________________________________________________________        Starting blocked                                                                       Starting 1-brom-                                                     4-oxycyclopent-                                                                        3-triphenylmethoxy-                                              Ex- 2-en-1-one of                                                                          1-trans-alkene of                                                ample                                                                             Example  Example   Product 8-methylprostenoic acid                        __________________________________________________________________________    1354                                                                              95       1175      8β-methyl-9-oxo-11α,15-dihydroxy-16,16-                            N                                                                             dimethyl-13-trans-prostenoic acid                                             8α-methyl-9-oxo-11α,15-dihydroxy-16,16-                           O                                                                             dimethyl-8-iso-13-trans-prostenoic acid                                       8β-methyl-9-oxo-11α,15-dihydroxy-16,16-                            dimethyl-13-cis-prostenoic acid                                               8α-methyl-9-oxo-11α,15-dihydroxy-16,16-                           dimethyl-8-iso-13-cis-prostenoic acid                  1355                                                                              95       1178      8β-methyl-9-oxo-11α,15-dihydroxy,17,17-                            dimethyl-13-trans-prostenoic acid                                             8α-methyl-9-oxo-11α,15-dihydroxy-17,17-                           dimethyl-8-iso-13-trans-prostenoic acid                                       8β-methyl-9-oxo-11α,15-dihydroxy-17,17-                            dimethyl-13-cis-prostenoic acid                                               8α-methyl-9-oxo-11α,15-dihydroxy-17,17-                           dimethyl-8-iso-13-cis-prostenoic acid                  1356                                                                              95       1182      8β-methyl-9-oxo-11α,15-dihydroxy-13-tran                           s,                                                                            17-cis-prostadienoic acid                                                     8α-methyl-9-oxo-11α,15-dihydroxy-8-iso-                           13-                                                                           trans,17-cis-prostadienoic acid                                               8β-methyl-9-oxo-11α,15-dihydroxy-13-cis,                           17-cis-prostadienoic acid                                                     8α-methyl-9-oxo-11α,15-dihydroxy-8-iso-                           13-                                                                           cis,17-cis-prostadienoic acid                          1357                                                                              95       1185      8β-methyl-9-oxo-11α,15-dihydroxy-20-ethy                           l-                                                                            13-trans-prostenoic acid                                                      8α-methyl-9-oxo-11α,15-dihydroxy-20-eth                           yl-                                                                           8-iso-13-trans-prostenoic acid                                                8β-methyl-9-oxo-11α,15-dihydroxy-20-ethy                           l-                                                                            13-cis-prostenoic acid                                                        8α-methyl-9-oxo-11α,15-dihydroxy-20-eth                           yl-                                                                           8-iso-13-cis-prostenoic acid                           1358                                                                              1327     728       8β-methyl-9-oxo-11α,15-dihydroxy-6,7-din                           or-                                                                           13-trans-prostenoic acid                                                      8α-methyl-9-oxo-11α,15-dihydroxy-6,7-di                           nor-                                                                          8-iso-13-trans-prostenoic adic                                                8β-methyl-9-oxo-11α,15-dihydroxy-6,7-din                           or-                                                                           13-cis-prostenoic acid                                                        8α-methyl-9-oxo-11α,15-dihydroxy-6,7-di                           nor-                                                                          8-iso-13-cis-prostenoic acid                           1359                                                                              1328     1186      8β-methyl-9-oxo-11α,15-dihydroxy-5,6,7-t                           ri-                                                                           nor-20-methyl-13-trans-prostenoic acid                                        8α-methyl-9-oxo-11α,15-dihydroxy-5,6,7-                           tri-                                                                          nor-20-methyl-8-iso-13-trans-prostenoic acid                                  8β-methyl-9-oxo-11α,15-dihydroxy-5,6,7-t                           ri-                                                                           nor-20-methyl-13-cis-prostenoic acid                                          8α-methyl-9-oxo-11α,15-dihydroxy-5,6,7-                           tri-                                                                          nor-20-methyl-8-iso-13-prostenoic acid                 1360                                                                              1329     728       8β-methyl-9-oxo-11α,15-dihydroxy-7a,7b-b                           is-                                                                           homo-13-trans-prostenoic acid                                                 8α-methyl-9-oxo-11α,15-dihydroxy-7a,7b-                           bis-                                                                          homo-8-iso-13-trans-prostenoic acid                                           8β-methyl-9-oxo-11α,15-dihydroxy-7a,7b-b                           is-                                                                           homo-13-cis-prostenoic acid                                                   8α-methyl-9-oxo-11α,15-dihydroxy-7a,7b-                           bis-                                                                          homo-8-iso-13-cis-prostenoic acid                      1361                                                                              1330     728       8β-methyl-9-oxo-11α,15-dihydroxy-2-ethyl                           -13-                                                                          trans-prostenoic acid                                                         8α-methyl-9-oxo-11α,15-dihydroxy-2-ethy                           l-8-                                                                          iso-13-trans-prostenoic acid                                                  8β-methyl-9-oxo-11α,15-dihydroxy-2-ethyl                           -13-                                                                          cis-prostenoic acid                                                           8α-methyl-9-oxo-11α,15-dihydroxy-2-ethy                           l-8-                                                                          iso-13-cis-prostenoic acid                             1362                                                                              1331     1186      8β-methyl-9-oxo-11α,15-dihydroxy-3,3,20-                           tri-                                                                          methyl-13-trans-prostenoic acid                                               8α-methyl-9-oxo-11α,15-dihydroxy-3,3,20                           -tri-                                                                         methyl-8-iso-13-trans-prostenoic acid                                         8β-methyl-9-oxo-11α,15-dihydroxy-3,3,20-                           tri-                                                                          methyl-13-cis-prostenoic acid                                                 8α-methyl-9-oxo-11α,15-dihydroxy-3,3,20                           -tri-                                                                         methyl-8-iso-13-cis-prostenoic acid                    1363                                                                              1332     728       8β-methyl-9-oxo-11α,15-dihydroxy-3-oxa-1                           3-                                                                            trans-prostenoic acid                                                         8α-methyl-9-oxo-11α,15-dihydroxy-3-oxa-                           8-iso-                                                                        13-trans-prostenoic acid                                                      8β-methyl-9-oxo-11α,15-dihydroxy-3-oxa-1                           3-                                                                            cis-prostenoic acid                                                           8α-methyl-9-oxo-11α,15-dihydroxy-3-oxa-                           8-                                                                            iso-13-cis-prostenoic acid                             1364                                                                              1332     1175      8β-methyl-9-oxo-11α,15-dihydroxy-3-oxa-1                           6,16-                                                                         dimethyl-13-trans-prostenoic acid                                             8α-methyl-9-oxo-11α,15-dihydroxy-3-oxa-                           16,16-                                                                        dimethyl-8-iso-13-trans-prostenoic acid                                       8β-methyl-9-oxo-11α,15-dihydroxy-3-oxa-1                           6,16-                                                                         dimethyl-13-cis-prostenoic acid                                               8α-methyl-9-oxo-11α,15-dihydroxy-3-oxa-                           16,16-                                                                        dimethyl-8-iso-13-cis-prostenoic acid                  1365                                                                              1332     1182      8β-methyl-9-oxo-11α,15-dihydroxy-3-oxa-1                           3-                                                                            trans,17-cis-prostadienoic acid                                               8α-methyl-9-oxo-11α,15-dihydroxy-3-oxa-                           8-iso-                                                                        13-trans,17-cis-prostadienoic acid                                            8β-methyl-9-oxo-11α,15-dihydroxy-3-oxa-1                           3-                                                                            cis,17-cis-prostadienoic acid                                                 8α-methyl-9-oxo-11α,15-dihydroxy-3-oxa-                           8-iso-                                                                        13-cis,17-cis-prostadienoic acid                       1366                                                                              1332     1185      8β-methyl-9-oxo-11α,15-dihydroxy-3-oxa-2                           0-                                                                            ethyl-13-trans-prostenoic acid                                                8α-methyl-9-oxo-11α,15-dihydroxy-3-oxa-                           20-                                                                           ethyl-8-iso-13-trans-prostenoic acid                                          8β-methyl-9-oxo-11α,15-dihydroxy-3-oxa-2                           0-                                                                            ethyl-13-cis-prostenoic acid                                                  8α-methyl-9-oxo-11α,15-dihydroxy-3-oxa-                           20-                                                                           ethyl-8-iso-13-cis-prostenoic acid                     1367                                                                              1333     1178      8β-methyl-9-oxo-11α,15-dihydroxy-2-fluor                           o-                                                                            17,17-dimethyl-13-trans-prostenoic acid                                       8α-methyl-9-oxo-11α,15-dihydroxy-2-fluo                           ro-                                                                           17,17-dimethyl-8-iso-13-trans-prostenoic acid                                 8β-methyl-9-oxo-11α,15-dihydroxy-2-fluor                           o-                                                                            17,17-dimethyl-13-cis-prostenoic acid                                         8α-methyl-9-oxo-11α,15-dihydroxy-2-fluo                           ro-                                                                           17,17-dimethyl-8-iso-13-cis-prostenoic acid            1368                                                                              1334     728       8β-methyl-9-oxo-11α,15-dihydroxy-7-nor-1                           3-                                                                            trans-prostenoic acid                                                         8α-methyl-9-oxo-11α,15-dihydroxy-7-nor-                           8-                                                                            iso-13-trans-prostenoic acid                                                  8β-methyl-9-oxo-11α,15-dihydroxy-7-nor-1                           3-                                                                            cis-prostenoic acid                                                           8α-methyl-9-oxo-11α,15-dihydroxy-7-nor-                           8-                                                                            iso-13-cis-prostenoic acid                             1369                                                                              1335     1175      8β-methyl-9-oxo-11α,15-dihydroxy-7a-homo                           -                                                                             16,16-dimethyl-13-trans-prostenoic acid                                       8α-methyl-9-oxo-11α,15-dihydroxy-7a-hom                           o-16,16-                                                                      dimethyl-8-iso-13-trans-prostenoic acid                                       8β-methyl-9-oxo-11α,15-dihydroxy-7a-homo                           -                                                                             16,16-dimethyl-13-cis-prostenoic acid                                         8α-methyl-9-oxo-11α,15-dihydroxy-7a-hom                           o-                                                                            16,16-dimethyl-8-iso-13-cis-prostenoic acid            1370                                                                              1336     728       8β-methyl-9-oxo-11α,15-dihydroxy-2-pheny                           l-                                                                            13-trans-prostenoic acid                                                      8α-methyl-9-oxo-11α,15-dihydroxy-2-phen                           yl-                                                                           8-iso-13-trans-prostenoic acid                                                8β-methyl-9-oxo-11α,15-dihydroxy-2-pheny                           l-                                                                            13-cis-prostenoic acid                                                        8α-methyl-9-oxo-11α,15-dihydroxy-2-phen                           yl-                                                                           8-iso-13-cis-prostenoic acid                           1371                                                                              1337     1182      8β-methyl-9-oxo-11α,15-dihydroxy-2-methy                           l-                                                                            13-trans,17-cis-prostadienoic acid                                            8α-methyl-9-oxo-11α,15-dihydroxy-2-meth                           yl-                                                                           8-iso-13-trans,17-cis-prostadienoic acid                                      8β-methyl-9-oxo-11α,15-dihydroxy-2-methy                           l-                                                                            13-cis,17-cis-prostadienoic acid                                              8α-methyl-9-oxo-11α,15-dihydroxy-2-meth                           yl-                                                                           8-iso-13-cis,17-cis-prostadienoic acid                 1372                                                                              1121     728       8β-methyl-9-oxo-11α,15-dihydroxy-5-cis,1                           3-                                                                            trans-prostadienoic acid                                                      8α-methyl-9-oxo-11α,15-dihydroxy-8-iso-                           5-                                                                            cis,13-trans-prostadienoic acid                                               8β-methyl-9-oxo-11α,15-dihydroxy-5-cis,1                           3-                                                                            cis-prostadienoic acid                                                        8α-methyl-9-oxo-11α,15-dihydroxy-8-iso-                           5-                                                                            cis,13-cis-prostadienoic acid                          1373                                                                              1121     1182      8β-methyl-9-oxo-11α,15-dihydroxy-5-cis,1                           3-                                                                            trans,17-cis-prostatrienoic acid                                              8α-methyl-9-oxo-11α,15-dihydroxy-8-iso-                           5                                                                             cis,13-trans,17-cis-prostatrienoic acid                                       8β-methyl-9-oxo-11α,15-dihydroxy-5-cis,                            y                                                                             13-cis,17-cis-prostatrienoic acid                                             8α-methyl-9-oxo-11α,15-dihydroxy-8-iso-                           0                                                                             5-cis,13-cis,17-cis-prostatrienoic acid                1374                                                                              1121     1175      8β-methyl-9-oxo-11α,15-dihydroxy-16,16-d                           i-                                                                            methyl-5-cis,13-trans-prostadienoic acid                                      8α-methyl-9-oxo-11α,15-dihydroxy-16,16-                           di-                                                                           methyl-8-iso-5-cis,13-trans-prostadienoic acid                                8β-methyl-9-oxo-11α,15-dihydroxy-16,16-d                           i-                                                                            methyl-5-cis,13-cis-prostadienoic acid                                        8α-methyl-9-oxo-11α,15-dihydroxy-16,16-                           di-                                                                           methyl-8-iso-5-cis,13-cis-prostadienoic acid           1375                                                                              1122     1186      8β-methyl-9-oxo-11α,15-dihydroxy-4-nor-2                           0-                                                                            methyl-5-cis,13-trans-prostadienoic acid                                      8α-methyl-9-oxo-11α,15-dihydroxy-4-nor-                           20-                                                                           methyl-8-iso-5-cis,13-trans-prostadienoic acid                                8β-methyl-9-oxo-11α,15-dihydroxy-4-nor-2                           0-                                                                            methyl-5-cis,13-cis-prostadienoic acid                                        8β-methyl-9-oxo-11α,15-dihydroxy-4-nor-2                           0-                                                                            methyl-8-iso-5-cis,13-cis-prostadienoic acid           1376                                                                              1123     1178      8β-methyl-9-oxo-11α,15-dihydroxy-4a-homo                           -17,                                                                          17-dimethyl-5-cis,13-trans-prostadienoic acid                                 8α-methyl-9-oxo-11α,15-dihydroxy-4a-hom                           o-17,                                                                         17-dimethyl-8-iso-5-cis,13-cis-prostadienoic                                  acid                                                                          8β-methyl-9-oxo-11α,15-dihydroxy-4a-homo                           -17,                                                                          17-dimethyl-5-cis,13-cis-prostadienoic acid                                   8α-methyl-9-oxo-11α,15-dihydroxy-4a-hom                           o-17,                                                                         17-dimethyl-8-iso-5-cis,13-cis-prostadienoic                                  acid                                                   1377                                                                              1124     1185      8β-methyl-9-oxo-11α,15-dihydroxy-4a,4b-b                           is-                                                                           homo-20-ethyl-5-cis,13-trans-prostadienoic                                    acid                                                                          8α-methyl-9-oxo-11α,15-dihydroxy-4a,4b-                           bis-                                                                          homo-20-ethyl-8-iso-5-cis,13-trans-prosta-                                    dienoic acid                                                                  8β-methyl-9-oxo-11α,15-dihydroxy-4a,4b-b                           is-                                                                           homo-20-ethyl-5-cis,13-cis-prostadienoic acid                                 8α-methyl-9-oxo-11α,15-dihydroxy-4a,4b-                           bis-                                                                          homo-20-ethyl-8-iso-5-cis,13-cis-prosta-                                      dienoic acid                                           1378                                                                              1124     1182      8β-methyl-9-oxo-11α,15-dihydroxy-4a,4b-b                           is-                                                                           homo-5-cis,13-trans,17-cis-prostatrienoic                                     acid                                                                          8α-methyl-9-oxo-11α,15-dihydroxy-4a,4b-                           bis-                                                                          homo-8-iso-5-cis,13-trans,17-cis-prosta-                                      trienoic acid                                                                 8β-methyl-9-oxo-11α,15-dihydroxy-4a,4b-b                           is-                                                                           homo-5-cis,13-cis,17-cis-prostatrienoic acid                                  8α-methyl-9-oxo-11α,15-dihydroxy-4a,4b-                           bis-                                                                          homo-8-iso-5-cis,13,cis-17-cis-prostatrienoic                                 acid                                                   1379                                                                              1339     1186      Methyl 8β-methyl-9-oxo-11α,15-dihydroxy-                           20-                                                                           methyl-13-trans-prostenoate                                                   Methyl 8α-methyl-9-oxo-11α,15-dihydroxy                           -20-                                                                          methyl-8-iso-13-trans-prostenoate                                             Methyl 8β-methyl-9-oxo-11α,15-dihydroxy-                           20-                                                                           methyl-13-cis-prostenoate                                                     Methyl 8α-methyl-9-oxo-11α,15-dihydroxy                           -20-                                                                          methyl-8-iso-13-cis-prostenoate                        1380                                                                              1342     1182      Ethyl 8β-methyl-9-oxo-11α,15-dihydroxy-7                           a,7b-                                                                         bishomo-13-trans,17-cis-prostadienoate                                        Ethyl 8α-methyl-9-oxo-11α,15-dihydroxy-                           7a,7b-                                                                        bishomo-8-iso-13-trans,17-cis-prostadienoate                                  Ethyl 8β-methyl-9-oxo-11α,15-dihydroxy-7                           a,7b-                                                                         bishomo-13-cis,17-cis-prostadienoate                                          Ethyl 8α-methyl-9-oxo-11α,15-dihydroxy-                           7a,7b-                                                                        bishomo-8-iso-13-cis,17-cis-prostadienoate             1381                                                                              1343     1175      Ethyl 8β-methyl-9-oxo-11α,15-dihydroxy-2                           -                                                                             ethyl-16,16-dimethyl-13-trans-prostenoate                                     Ethyl 8α-methyl-9-oxo-11α,15-dihydroxy-                           2-                                                                            ethyl-16,16-dimethyl-8-iso-13-trans-                                          prostenoate                                                                   Ethyl 8β -methyl-9-oxo-11α,15-dihydroxy-                           2-                                                                            ethyl-16,16-dimethyl-13-cis-prostenoate                                       Ethyl 8α-methyl-9-oxo-11α,15-dihydroxy-                           2-                                                                            ethyl-16,16-dimethyl-8-iso-13-cis-prostenoate          1382                                                                              1344     1178      Ethyl 8β-methyl-9-oxo-11α,15-dihydroxy-3                           ,3-                                                                           17,17-tetramethyl-13-trans-prostenoate                                        Ethyl 8α-methyl-9-oxo-11α,15-dihydroxy-                           3,3-                                                                          17,17-tetramethyl-8-iso-13-trans-prostenoate                                  Ethyl 8β-methyl-9-oxo-11α,15-dihydroxy-3                           ,3-                                                                           17,17-tetramethyl-13-cis-prostenoate                                          Ethyl 8α-methyl-9-oxo-11α,15-dihydroxy-                           3,3-                                                                          17,17-tetramethyl-8-iso-13-cis-prostenoate             1383                                                                              1345     1178      Ethyl 8β-methyl-9-oxo-11α,15-dihydroxy-3                           -oxa-                                                                         17,17-dimethyl-13-trans-prostenoate                                           Ethyl 8α-methyl-9-oxo-11α,15-dihydroxy-                           3-oxa-                                                                        17,17-dimethyl-8-iso-13-trans-prostenoate                                     Ethyl 8β-methyl-9-oxo-11α,15-dihydroxy-3                           -oxa-                                                                         17,17-dimethyl-13-cis-prostenoate                                             Ethyl 8α-methyl-9-oxo-11α,15-dihydroxy-                           3-oxa-                                                                        17,17-dimethyl-8-iso-13-cis-prostenoate                1384                                                                              1350     728       Butyl 8β-methyl-9-oxo-11α,15-dihydroxy-1                           3-                                                                            trans-prostenoate                                                             Butyl 8α-methyl-9-oxo-11α,15-dihydroxy-                           8-iso-                                                                        13-trans-prostenoate                                                          Butyl 8β-methyl-9-oxo-11α,15-dihydroxy-1                           3-                                                                            cis-prostenoate                                                               Butyl 8α-methyl-9-oxo-11α,15-dihydroxy-                           8-iso-                                                                        13-cis-prostenoate                                     1385                                                                              1352     1182      Decyl 8β-methyl-9-oxo-11α,15-dihydroxy-                            13-trans,17-cis-prostadienoate                                                Decyl 8α-methyl-9-oxo-11α,15-dihydroxy-                           8-iso-                                                                        13-trans,17-cis-prostadienoate                                                Decyl 8β-methyl-9-oxo-11α,15-dihydroxy-1                           3-                                                                            cis-17-cis-prostadienoate                                                     Decyl 8α-methyl-9-oxo-11α,15-dihydroxy-                           8-iso-                                                                        13-cis,17-cis-prostadienoate                           1386                                                                              1301     728       Ethyl 8β-methyl-9-oxo-11α-acetoxy-15-hyd                           roxy-                                                                         13-trans-prostenoate                                                          Ethyl 8α-methyl-9-oxo-11α-acetoxy-15-hy                           droxy-                                                                        8-iso-13-trans-prostenoate                                                    Ethyl 8β-methyl-9-oxo-11α-acetoxy-15-hyd                           roxy-                                                                         13-cis-prostenoate                                                            Ethyl 8α-methyl-9-oxo-11α-acetoxy-15-hy                           droxy-                                                                        8-iso-13-cis-prostenoate                               __________________________________________________________________________

EXAMPLE 1387 Preparation of 8β-methyl-prostaglandin A₁

A mixture of 0.30 g. of 8β-methyl-prostaglandin E₁ (Example 1353) and 10ml. of 1:9 aqueous acetic acid is heated to 65° C. for 18 hours under aninert atmosphere. The solvent is removed in vacuo and the residue ispurified upon Silic AR-CC-4® using a benzene-ethylacetate gradient toyield the title compound.

EXAMPLES 1388-1522

Treatment of the designated 8-methyl-9-oxo-1-dihydroxy-prostenoic acidderivatives of Table 41 below with 1:9 aqueous acid and purification allas described in Example 1387 gives the corresponding8-methyl-9-oxo-10,13-prostadienoic acids and esters of the table.

                  TABLE 41                                                        ______________________________________                                                Starting 9-oxo- Product 8-methyl-9-oxo-                               Exam-   11-hydroxy      10,13-prostadienoic                                   ple     derivative      acids or esters                                       ______________________________________                                        1388    8α-methyl-8-iso-                                                                        8α-methyl-8-iso-prosta-                                 prostaglandin   glandin A.sub.1                                               E.sub.1 (Example 1353)                                                1389    8β-methyl-9-oxo-                                                                         8β-methyl-11α,15-dihy-                             11α, 15-dihy-                                                                           droxy-10,13-cis-prosta-                                       droxy-13-cis-   dienoic acid                                                  prostenoic acid                                                               (Example 1353)                                                        1390    8α-methyl-9-oxo-                                                                        8α-methyl-11α,15-dihy-                            11α,15-dihy-                                                                            droxy-8-iso-10,13-cis-                                        droxy-8-iso-13- prostadienoic acid                                            cis-prostenoic                                                                acid (Example                                                                 1353)                                                                 1391    8β-methyl-9-oxo-                                                                         8β-methyl-9-oxo-15-hy-                                   11α,15-dihy-                                                                            droxy-16,16-dimethyl                                          droxy-16,16-di- 10,13-trans-prostadie-                                        methyl-13-trans-                                                                              noic acid                                                     prostenoic acid                                                               (Example 1354)                                                        1392    8α-methyl-9-oxo-                                                                        8α-methyl-9-oxo-15-hy-                                  11α,15-dihy-                                                                            droxy-16,16-dimethyl-                                         droxy-16,16-di- 8-iso-10,13-trans-pro-                                        methyl-8-iso-13-                                                                              stadienoic acid                                               trans-proste-                                                                 noic acid (Exam-                                                              ple 1354)                                                             1393    8β-methyl-9-oxo-                                                                         8β-methyl-9-oxo-15-hy-                                   11α,15-dihydro-                                                                         droxy-16,16-dimethyl                                          xy-16,16-di-    10,13-cis-prostadienoic                                       methyl-13-cis-  acid                                                          prostenoic acid                                                               (Example 1354)                                                        1394    8α-methyl-9-oxo-                                                                        8α-methyl-9-oxo-15-hy-                                  11α,15-dihydro-                                                                         droxy-16,16-dimethyl-                                         xy-16,16-di-    8-iso-10,13-cis-pro-                                          methyl-8-iso-13-                                                                              stadienoic acid                                               cis-prostenoic                                                                acid (Example                                                                 1354                                                                  1395    8β-methyl-9-oxo-                                                                         8β-methyl-9-oxo-15-hy-                                   11α,15-dihydro-                                                                         droxy-17,17-dimethyl                                          xy-17,17-di-    10,13-trans-prostadie-                                        methyl 13-trans-                                                                              noic acid                                                     prostenoic acid                                                               (Example 1355)                                                        1396    8α-methyl-9-oxo-                                                                        8α-methyl-9-oxo-15-hy                                   11α,15-dihydro-                                                                         droxy-17,17-dimethyl-                                         xy-17,17-di-    8-iso-10,13-trans-pro-                                        methyl-8-iso-13-                                                                              stadienoic acid                                               trans-prostenoic                                                              acid (Example                                                                 1355)                                                                 1397    8β-methyl-9-oxo-                                                                         8β-methyl-9-oxo-15-hy-                                   11α,15-dihydro-                                                                         droxy-17,17-dimethyl                                          xy-17,17-di-    10,13-cis-prostadie-                                          methyl 13-cis-  noic acid                                                     prostenoic acid                                                               (Example 1355)                                                        1398    8α-methyl-9-oxo-                                                                        8α-methyl-9-oxo-15-hy-                                  11α,15-dihydro-                                                                         droxy-17,17-dimethyl-                                         xy-17,17-di-    8-iso-10,13-cis-pro-                                          methyl-8-iso-13-                                                                              stadienoic acid                                               cis-prostenoic                                                                acid (Example                                                                 1355)                                                                 1399    8β-methyl-9-oxo-                                                                         8β-methyl-9-oxo-15-hy-                                   11α,15-dihydro-                                                                         droxy-10,13-trans,17-                                         xy-13-trans,17- cis-prostatrienoic                                            cis-prostadi-   acid                                                          enoic acid                                                                    (Example 1356)                                                        1400    8α-methyl-9-oxo-                                                                        8α-methyl-9-oxo-15-hy-                                  11α,15-dihydro-                                                                         droxy-8-iso-10,13-trans,-                                     xy-8-iso-13-    17-cis-prostatrienoic                                         trans,17-cis-   acid                                                          prostadienoic                                                                 acid (Example                                                                 1356)                                                                 1401    8β-methyl-9-oxo-                                                                         8β-methyl-9-oxo-15-hy-                                   11α,15-dihydro-                                                                         droxy-10,13-cis,17-cis-                                       xy-13-cis,17-cis,-                                                                            prostatrienoic acid                                           prostadienoic                                                                 acid (Example                                                                 1356)                                                                 1402    8α-methyl-9-oxo-                                                                        8α-methyl-9-oxo-15-hy                                   11α,15-dihydro-                                                                         droxy-8-iso-10,13-cis,-                                       xy-8-iso-13-cis-                                                                              17-cis-prostatrienoic                                         17-cis-prostadi-                                                                              acid                                                          enoic acid                                                                    (Example 1356)                                                        1403    8β-methyl-9-oxo-                                                                         8β-methyl-9-oxo-15-hy-                                   11α,15-dihydro-                                                                         droxy-20-ethyl-10,13-                                         xy-20-ethyl-13- trans-prostadienoic                                           trans-proste-   acid                                                          noic acid (Exam-                                                              ple 1357                                                              1404    8α-methyl-9-oxo-                                                                        8α-methyl-9-oxo-15-hy-                                  11α,15-dihydro-                                                                         droxy-20-ethyl-8-iso-                                         xy-20-ethyl-8-  10,13-trans-prostadi-                                         iso-13-trans-   enoic acid                                                    prostenoic acid                                                               (Example 1357)                                                        1405    8β-methyl-9-oxo-                                                                         8β -methyl-9-oxo-15-hy-                                  11α,15-dihydro-                                                                         droxy-20-ethyl-10,13-                                         xy-20-ethyl-13- cis-prostadienoic acid                                        cis-prostenoic                                                                acid (Example                                                                 1357                                                                  1406    8α-methyl-9-oxo-                                                                        8α-methyl-9-oxo-15-hy-                                  11α,15-dihydro-                                                                         droxy-20-ethyl-8-iso-                                         xy-20-ethyl-8-  10,13-cis-prostadie-                                          iso-13-cis-pro- noic acid                                                     stenoic acid                                                                  (Example 1357)                                                        1407    8β-methyl-9-oxo-                                                                         8β-methyl-9-oxo-15-hy-                                   11α,15-dihydro-                                                                         droxy-6,7-dinor-10,13-                                        xy-6,7-dinor-13-                                                                              trans-prostadienoic                                           trans-proste-   acid                                                          noic acid (Exam-                                                              ple 1358)                                                             1408    8α-methyl-9-oxo-                                                                        8α-methyl-9-oxo-15-hy-                                  11α,15-dihydro-                                                                         droxy-6,7,dinor-8-iso-                                        xy-6,7-dinor-8- 10,13-trans-prostadie-                                        iso-13-trans-   noic acid                                                     prostenoic acid                                                               (Example 1358)                                                        1409    8β-methyl-9-oxo                                                                          8β-methyl-9-oxo-15-hy-                                   11α,15-dihydro-                                                                         droxy-6,7-dinor-10,13-                                        xy-6,7-dinor-13-                                                                              cis-prostadienoic acid                                        cis-prostenoic                                                                acid (Example                                                                 1358)                                                                 1410    8α-methyl-9-oxo-                                                                        8α-methyl-9-oxo-15-hy-                                  11α,15-dihydro-                                                                         droxy-6,7-dinor-8-iso-                                        xy-6,7-dinor-8- 10,13-cis-prostadie-                                          iso-13-cis-pro- noic acid                                                     stenoic acid                                                                  (Example 1558)                                                        1411    8β-methyl-9-oxo-                                                                         8β-methyl-9-oxo-15-hy-                                   11α,15-dihydro-                                                                         droxy-5,6,7-trinor-20-                                        xy-5,6,7-trinor-                                                                              methyl 10,13-trans-                                           20-methyl 13-   prostadienoic acid                                            trans-prostenoic                                                              acid (Example                                                                 1359)                                                                 1412    8α-methyl-9-oxo-                                                                        8α-methyl-9-oxo-15-hy-                                  11α,15-dihydro-                                                                         droxy-5,6,7-trinor-20-                                        xy-5,6,7-trinor-                                                                              methyl-8-iso-10,13-                                           20-methyl-8-iso-                                                                              trans-prostadienoic                                           13-trans-pro-   acid                                                          stenoic acid                                                                  (Example 1359)                                                        1413    8β-methyl-9-oxo-                                                                         8β-methyl-9-oxo-15-hy-                                   11α,15-dihydro-                                                                         droxy-5,6,7-trinor-20-                                        xy-5,6,7-trinor-                                                                              methyl 10,13-cis-pro-                                         20-methyl 13-   stadienoic acid                                               cis-prostenoic                                                                acid (Example                                                                 1359)                                                                 1414    8α -methyl-9-oxo-                                                                       8α-methyl-9-oxo-15-hy-                                  11α,15-dihydro-                                                                         droxy-5,6,7-trinor-20-                                        xy-5,6,7-trinor-                                                                              methyl-8-iso-10,13-                                           20-methyl-8-    cis-prostadienoic acid                                        iso-13-cis-pro-                                                               stenoic acid                                                                  (Example 1359)                                                        1415    8β-methyl-9-oxo-                                                                         8β-methyl-9-oxo-15-hy-                                   11α,15-dihydro-                                                                         droxy-7a,7b-bishomo-                                          xy-7a,7b-bishomo-                                                                             10,13-trans-prostadie-                                        13-trans-pro-   noic acid                                                     stenoic acid                                                                  (Example 1360)                                                        1416    8α-methyl-9-oxo-                                                                        8α-methyl-9-oxo-15-hy-                                  11α,15-dihydro-                                                                         droxy-7a,7b-bishomo-                                          xy-7a,7b-bishomo-                                                                             8-iso-10,13-trans-                                            8-iso-13-trans- prostadienoic acid                                            prostenoic acid                                                               (Example 1360)                                                        1417    8β-methyl-9-oxo-                                                                         8β-methyl-9-oxo-15-hy-                                   11α,15-dihydro-                                                                         droxy-7a,7b-bishomo-                                          xy-7a,7b-bishomo-                                                                             10,13-cis-prostadie-                                          13-cis-proste-  noic acid                                                     noic acid (Exam-                                                              ple 1360)                                                             1418    8α-methyl-9-oxo-                                                                        8α-methyl-9-oxo-15-hy-                                  11α,15-dihydro-                                                                         droxy-7a,7b-bishomo-                                          xy-7a,7b-bishomo-                                                                             8-iso-10,13-cis-pro-                                          8-iso-13-cis-   stadienoic acid                                               prostenoic acid                                                               (Example 1360)                                                        1419    8β-methyl-9-oxo-                                                                         8β-methyl-9-oxo-15-hy-                                   11α,15-dihydro-                                                                         droxy-2-ethyl-10,13-                                          xy-2-ethyl-13-  trans-prostadienoic                                           trans-proste-   acid                                                          noic acid (Exam-                                                              ple 1361)                                                             1420    8α-methyl-9-oxo-                                                                        8α-methyl-9-oxo-15-hy-                                  11α,15-dihydro-                                                                         droxy-2-ethyl-8-iso-                                          xy-2-ethyl-8-   10,13-trans-prostadi-                                         iso-13-trans-   enoic acid                                                    prostenoic acid                                                               (Example 1361)                                                        1421    8β-methyl-9-oxo-                                                                         8β-methyl-9-oxo-15-hy-                                   11α,15-dihydro-                                                                         droxy-2-ethyl-10,13-                                          xy-2-ethyl-13-  cis-prostadienoic acid                                        cis-prostenoic                                                                acid (Example                                                                 1361)                                                                 1422    8α-methyl-9-oxo-                                                                        8α-methyl-9-oxo-15-hy-                                  11α,15-dihydro-                                                                         droxy-2-ethyl-8-iso-                                          xy-2-ethyl-8-   10,13-cis-prostadie-                                          iso-13-cis-pro- noic acid                                                     stenoic acid                                                                  (Example 1361)                                                        1423    8β-methyl-9-oxo-                                                                         8β-methyl-9-oxo-15-hy-                                   11α,15-dihydro-                                                                         droxy-3,3,20-trimethyl-                                       xy-3,3,20-tri-  10,13-trans-prostadi-                                         methyl-13-trans-                                                                              enoic acid                                                    prostenoic acid                                                               (Example 1362)                                                        1424    8α-methyl-9-oxo-                                                                        8α-methyl-9-oxo-15-hy-                                  11α,15-dihydro-                                                                         droxy-3,3,20-trimethyl-                                       xy-3,3,20-tri-  8-iso-10,13-trans-pro-                                        methyl-8-iso-13-                                                                              stadienoic acid                                               trans-proste-                                                                 noic acid                                                                     (Example 1362)                                                        1425    8β-methyl-9-oxo-                                                                         8β-methyl-9-oxo-15-hy-                                   11α,15-dihydro-                                                                         droxy-3,3,20-trimethyl-                                       xy-3,3,20-tri-  10,13-cis-prostadie-                                          methyl-13-cis-  noic acid                                                     prostenoic acid                                                               (Example 1362)                                                        1426    8α-methyl-9-oxo-                                                                        8α-methyl-9-oxo-15-hy-                                  11α,15-dihydro-                                                                         droxy-3,3,20-trimethyl-                                       xy-3,3,20-tri-  8-iso-10,13-cis-pro-                                          methyl-8-iso-13-                                                                              stadienoic acid                                               cis-prostenoic                                                                acid (Example                                                                 1362)                                                                 1427    8β-methyl-9-oxo-                                                                         8β-methyl-9-oxo-15-hy-                                   11α,15-dihydro-                                                                         droxy-3-oxa-10,13-trans-                                      xy-3-oxa-13-    prostadienoic acid                                            trans-proste-                                                                 noic acid (Exam-                                                              ple 1363)                                                             1428    8α-methyl-9-oxo-                                                                        8α-methyl-9-oxo-15-hy-                                  11α,15-dihydro-                                                                         droxy-3-oxa-8-iso-10,-                                        xy-3-oxa-8-iso- 13,trans-prostadienoic                                        13-trans-proste-                                                                              acid                                                          noic acid (Exam-                                                              ple 1363)                                                             1429    8β-methyl-9-oxo-                                                                         8β-methyl-9-oxo-15-hy-                                   11α,15-dihydro-                                                                         droxy-3-oxa-10,13-cis-                                        xy-3-oxa-13-cis-                                                                              prostadienoic acid                                            prostenoic acid                                                               (Example 1363)                                                        1430    8α-methyl-9-oxo-                                                                        8α-methyl-9-oxo-15-hy-                                  11α,15-dihydro-                                                                         droxy-3-oxa-8-iso-10,-                                        xy-3-oxa-8-iso- 13-cis-prostadienoic                                          13-cis-proste-  acid                                                          noic acid (Exam-                                                              ple 1363)                                                             1431    8β-methyl-9-oxo-                                                                         8β-methyl-9-oxo-15-hy-                                   11α,15-dihydro-                                                                         droxy-3-oxa-16,16-di-                                         xy-3-oxa-16,16- methyl-10,13-trans-pro-                                       dimethyl-13-    stadienoic acid                                               trans-proste-                                                                 noic acid (Exam-                                                              ple 1364                                                              1432    8α -methyl-9-oxo-                                                                       8α-methyl-9-oxo-15-hy-                                  11α,15-dihydro-                                                                         droxy-3-oxa-16,16-di-                                         xy-3-oxa-16,16- methyl-8-iso-10,13-                                           dimethyl-8-iso- trans-prostadienoic                                           13-trans-proste-                                                                              acid                                                          noic acid (Exam-                                                              ple 1364)                                                             1433    8β-methyl-9-oxo-                                                                         8β-methyl-9-oxo-15-hy-                                   11α,15-dihydro-                                                                         droxy-3-oxa-16,16-di-                                         xy-3-oxa-16,16- methyl-10,13-cis-pro-                                         dimethyl-13-cis-                                                                              stadienoic acid                                               prostenoic acid                                                               (Example 1364)                                                        1434    8α-methyl-9-oxo-                                                                        8α-methyl-9-oxo-15-hy-                                  11α,15-dihydro-                                                                         droxy-3-oxa-16,16-di-                                         xy-3-oxa-16,16- methyl-8-iso-10,13-cis-                                       dimethyl-8-iso- prostadienoic acid                                            13-cis-proste-                                                                noic acid (Exam-                                                              ple 1364)                                                             1435    8β-methyl-9-oxo-                                                                         8β-methyl-9-oxo-15-hy-                                   11α,15-dihydro-                                                                         droxy-3-oxa-10,13-                                            xy-3-oxa-13-    trans,17-cis-prosta-                                          trans,17-cis-   trienoic acid                                                 prostadienoic                                                                 acid (Example                                                                 1365                                                                  1436    8α-methyl-9-oxo-                                                                        8α-methyl-9-oxo-15-hy-                                  11α,15-dihydro-                                                                         droxy-3-oxa-8-iso-10,-                                        xy-3-oxa-8-iso- 13-trans,17-cis-pro-                                          13-trans,17-cis-                                                                              statrienoic acid                                              prostadienoic                                                                 acid (Example                                                                 1365)                                                                 1437    8β-methyl-9-oxo-                                                                         8β-methyl-9-oxo-15-hy-                                   11α,15-dihydro-                                                                         droxy-3-oxa-10,13-cis,-                                       xy-3-oxa-13-cis,-                                                                             17-cis-prostatrienoic                                         17-cis-prosta-  acid                                                          dienoic acid                                                                  (Example 1365)                                                        1438    8α-methyl-9-oxo-                                                                        8α-methyl-9-oxo-15-hy-                                  11α,15-dihydro-                                                                         droxy-3-oxa-8-iso-10,-                                        xy-3-oxa-8-iso- 13-cis,17-cis-prosta-                                         13-cis,17-cis-  trienoic acid                                                 prostadienoic                                                                 acid (Example                                                                 1365                                                                  1439    8β-methyl-9-oxo-                                                                         8β-methyl-9-oxo-15-hy-                                   11α,15-dihydro-                                                                         droxy-3-oxa-20-ethyl-                                         xy-3-oxa-20-    10,13-trans-prostadie-                                        ethyl-13-trans- noic acid                                                     prostenoic acid                                                               (Example 1366)                                                        1440    8α-methyl-9-oxo-                                                                        8α-methyl-9-oxo-15-hy-                                  11α,15-dihydro-                                                                         droxy-3-oxa-20-ethyl-                                         xy-3-oxa-20-    8-iso-10,13-trans-                                            ethyl-8-iso-13- prostadienoic acid                                            trans-proste-                                                                 noic acid (Exam-                                                              ple 1366)                                                             1441    8β-methyl-9-oxo-                                                                         8β-methyl-9-oxo-15-hy-                                   11α,15-dihydro-                                                                         droxy-3-oxa-20-ethyl-                                         xy-3-oxa-20-    10,13-cis-prostadie-                                          ethyl-13-cis-   noic acid                                                     prostenoic acid                                                               (Example 1366)                                                        1442    8α-methyl-9-oxo-                                                                        8α-methyl-9-oxo-15-hy-                                  11α,15-dihydro-                                                                         droxy-3-oxa-20-ethyl-                                         xy-3-oxa-20-    8-iso-10,13-cis-pro-                                          ethyl-8-iso-13- stadienoic acid                                               cis-prostenoic                                                                acid (Example                                                                 1366)                                                                 1443    8β-methyl-9-oxo-                                                                         8β-methyl-9-oxo-15-hy-                                   11α,15-dihydro-                                                                         droxy-2-fluoro-17,17-                                         xy-2-fluoro-17,-                                                                              dimethyl-10,13-trans-                                         17-dimethyl-13- prostadienoic acid                                            trans-proste-                                                                 noic acid (Exam-                                                              ple 1367)                                                             1444    8α-methyl-9-oxo-                                                                        8α-methyl-9-oxo-15-hy-                                  11α,15-dihydro-                                                                         droxy-2-fluoro-17,17-                                         xy-2-fluoro-17,-                                                                              dimethyl-8-iso-10,13-                                         17-dimethyl-8-  trans-prostadienoic                                           iso-13-trans-   acid                                                          prostenoic acid                                                               (Example 1367)                                                        1445    8β-methyl-9-oxo-                                                                         8β-methyl-9-oxo-15-hy-                                   11α,15-dihydro-                                                                         droxy-2-fluoro-17,17-                                         xy-2-fluoro-17,-                                                                              dimethyl-10,13-cis-                                           17-dimethyl-13- prostadienoic acid                                            cis-prostenoic                                                                acid (Example                                                                 1367)                                                                 1446    8α-methyl-9-oxo-                                                                        8α-methyl-9-oxo-15-hy-                                  11α,15-dihydro-                                                                         droxy-2-fluoro-17,17-                                         xy-2-fluoro-17,-                                                                              dimethyl-8-iso-10,13-                                         17-dimethyl-8-  cis-prostadienoic acid                                        iso-13-cis-pro-                                                               stenoic acid                                                                  (Example 1367)                                                        1447    8β-methyl-9-oxo-                                                                         8β-methyl-9-oxo-15-hy-                                   11α,15-dihydro-                                                                         droxy-7-nor-10,13-trans-                                      xy-7-nor-13-    prostadienoic acid                                            trans-proste-                                                                 noic acid (Exam-                                                              ple 1368)                                                             1448    8α-methyl-9-oxo-                                                                        8α-methyl-9-oxo-15-hy-                                  11α,15-dihydro-                                                                         droxy-7-nor-8-iso-10,-                                        xy-7-nor-8-iso- 13-trans-prostadienoic                                        13-trans-pro-   acid                                                          stenoic acid                                                                  (Example 1368)                                                        1449    8β-methyl-9-oxo-                                                                         8β-methyl-9-oxo-15-hy-                                   11α,15-dihydro-                                                                         droxy-7-nor-10,13-cis-                                        xy-7-nor-13-cis-                                                                              prostadienoic acid                                            prostenoic acid                                                               (Example 1368)                                                        1450    8α-methyl-9-oxo-                                                                        8α-methyl-9-oxo-15-hy-                                  11α,15-dihydro-                                                                         droxy-7-nor-8-iso-10,-                                        xy-7-nor-8-iso- 13-cis-prostadienoic                                          13-cis-proste-  acid                                                          noic acid (Exam-                                                              ple 1368)                                                             1451    8β-methyl-9-oxo-                                                                         8β-methyl-9-oxo-15-hy-                                   11α,15-dihydro-                                                                         droxy-7a-homo-16,16-                                          xy-7a-homo-16,- dimethyl-10,13-trans-                                         16-dimethyl-13- prostadienoic acid                                            trans-proste-                                                                 noic acid (Exam-                                                              ple 1369)                                                             1452    8α-methyl-9-oxo-                                                                        8α-methyl-9-oxo-15-hy-                                  11α,15-dihydro-                                                                         droxy-7a-homo-16,16-                                          xy-7a-homo-16,- dimethyl-8-iso-10,13-                                         16-dimethyl-8-  trans-prostadienoic                                           iso-13-trans-   acid                                                          prostenoic acid                                                               (Example 1369)                                                        1453    8β-methyl-9-oxo-                                                                         8β-methyl-9-oxo-15-hy-                                   11α,15-dihydro-                                                                         droxy-7a-homo-16,16-                                          xy-7a-homo-16,- dimethyl-10,13-cis-                                           16-dimethyl-13- prostadienoic acid                                            cis-prostenoic                                                                acid (Example                                                                 1369)                                                                 1454    8α-methyl-9-oxo-                                                                        8α-methyl-9-oxo-15-hy-                                  11α,15-dihydro-                                                                         droxy-7a-homo-16,16-                                          xy-7a-homo-16,- dimethyl-8-iso-10,13-                                         16-dimethyl-8-  cis-prostadienoic acid                                        iso-13-cis-pro-                                                               stenoic acid                                                                  (Example 1369)                                                        1455    8β-methyl-9-oxo-                                                                         8β-methyl-9-oxo-15-hy-                                   11α,15-dihydro-                                                                         droxy-2-phenyl-10,13-                                         xy-2-phenyl-13- trans-prostadienoic                                           trans-prostenoic                                                                              acid                                                          acid (Example                                                                 1370)                                                                 1456    8α-methyl-9-oxo-                                                                        8α-methyl-9-oxo-15-hy-                                  11α,15-dihydro-                                                                         droxy-2-phenyl-8-iso-                                         xy-2-phenyl-8-  10,13-trans-prostadi-                                         iso-13-trans-   enoic acid                                                    prostenoic acid                                                               (Example 1370)                                                        1457    8β-methyl-9-oxo-                                                                         8β-methyl-9-oxo-15-hy-                                   11α,15-dihydro-                                                                         droxy-2-phenyl-10,13-                                         xy-2-phenyl-13- cis-prostadienoic acid                                        cis-prostenoic                                                                acid (Example                                                                 1370)                                                                 1458    8α-methyl-9-oxo-                                                                        8α-methyl-9-oxo-15-hy-                                  11α,15-dihydro-                                                                         droxy-2-phenyl-8-iso-                                         xy-2-phenyl-8-  10,13-cis-prostadie-                                          iso-13-cis-pro- noic acid                                                     stenoic acid                                                                  (Example 1370)                                                        1459    8β-methyl-9-oxo-                                                                         8β-methyl-9-oxo-15-hy-                                   11α,15-dihydro-                                                                         droxy-2-methyl-10,13-                                         xy-2-methyl-13- trans,17-cis-prosta-                                          trans,17-cis-   trienoic acid                                                 prostadienoic                                                                 acid (Example                                                                 1371)                                                                 1460    8α-methyl-9-oxo-                                                                        8α-methyl-9-oxo-15-hy-                                  11α,15-dihydro-                                                                         droxy-2-methyl-8-iso-                                         xy-2-methyl-8-  10,13-trans,17-cis-                                           iso-13-trans,-  prostatrienoic acid                                           17-cis-prostadi-                                                              enoic acid                                                                    (Example 1371)                                                        1461    8β-methyl-9-oxo-                                                                         8β-methyl-9-oxo-15-hy-                                   11α,15-dihydro-                                                                         droxy-2-methyl-10,13-                                         xy-2-methyl-13- cis,17-cis-prostatri-                                         cis,17-cis-pro- enoic acid                                                    stadienoic acid                                                               (Example 1371)                                                        1462    8α-methyl-9-oxo-                                                                        8α-methyl-9-oxo-15-hy-                                  11α,15-dihydro-                                                                         droxy-2-methyl-8-iso-                                         xy-2-methyl-8-  10,13-cis,17-cis-pro-                                         iso-13-cis,17-  statrienoic acid                                              cis-prostadie-                                                                noic acid (Exam-                                                              ple 1371)                                                             1463    8β-methyl-9-oxo-                                                                         8β-methyl-9-oxo-15-hy-                                   11α,15-dihydro-                                                                         droxy-5,cis,10,13-trans-                                      xy-5,cis,13-    prostatrienoic acid                                           trans-prosta-                                                                 dienoic acid                                                                  (Example 1372)                                                        1464    8α-methyl-9-oxo-                                                                        8α-methyl-9-oxo-15-hy-                                  11α,15-dihydro-                                                                         droxy-8-iso-5,cis,10,-                                        xy-8-iso-5,cis,-                                                                              13-trans-prostatrienoic                                       13-trans-prosta-                                                                              acid                                                          dienoic acid                                                                  (Example 1372)                                                        1465    8β-methyl-9-oxo-                                                                         8β-methyl-9-oxo-15-hy-                                   11α,15-dihydro-                                                                         droxy-5,cis,10,13-cis-                                        xy-5,cis,13-cis-                                                                              prostatrienoic acid                                           prostadienoic                                                                 acid (Example                                                                 1372)                                                                 1466    8α-methyl-9-oxo-                                                                        8α-methyl-9-oxo-15-hy-                                  11α,15-dihydro-                                                                         droxy-8-iso-5,cis,10,13-                                      xy-8-iso-5,cis,-                                                                              cis-prostatrienoic acid                                       13-cis-prostadi-                                                              enoic acid                                                                    (Example 1372)                                                        1467    8β-methyl-9-oxo-                                                                         8β-methyl-9-oxo-15-hy-                                   11α,15-dihydro-                                                                         droxy-5-cis,10,13-                                            xy-5-cis,13-    trans,17-cis-prosta-                                          trans,17-cis-   tetraenoic acid                                               prostatrienoic                                                                acid (Example                                                                 1373)                                                                 1468    8α-methyl-9-oxo-                                                                        8α-methyl-9-oxo-15-hy-                                  11α,15-dihydro-                                                                         droxy-8-iso-5-cis,10,-                                        xy-8-iso-5-cis,-                                                                              13-trans,17-cis-prosta-                                       13-trans,17-cis-                                                                              tetraeneoic acid                                              prostatrienoic                                                                acid (Example                                                                 1373)                                                                 1469    8β-methyl-9-oxo-                                                                         8β-methyl-9-oxo-15-hy-                                   11α,15-dihydro-                                                                         droxy-5-cis,10,13-cis,-                                       xy-5-cis,13-cis,-                                                                             17-cis-prostatetrae-                                          17-cis-prosta-  neoic acid                                                    trienoic acid                                                                 (Example 1373)                                                        1470    8α-methyl-9-oxo-                                                                        8α-methyl-9-oxo-15-hy-                                  11α,15-dihydro-                                                                         droxy-8-iso-5-cis,10,-                                        xy-8-iso-5-cis,-                                                                              13-cis,17-cis-prostate-                                       13-cis,17-cis-  traeneoic acid                                                prostatrienoic                                                                acid (Example                                                                 1373)                                                                 1471    8β-methyl-9-oxo-                                                                         8β-methyl-9-oxo-15-hy-                                   11α,15-dihydro-                                                                         droxy-16,16-dimethyl-                                         xy-16,16-di-    5-cis,10,13-trans-pro-                                        methyl-5-cis,13-                                                                              statrienoic acid                                              trans-prostadi-                                                               enoic acid (Exam-                                                             ple 1374)                                                             1472    8α-methyl-9-oxo-                                                                        8α-methyl-9-oxo-15-hy-                                  11α,15-dihydro-                                                                         droxy-16,16-dimethyl-                                         xy-16,16-di-    8-iso-5-cis,10,13-                                            methyl-8-iso-5- trans-prostatrienoic                                          cis,13-trans-   acid                                                          prostadienoic                                                                 acid (Example                                                                 1374)                                                                 1473    8β-methyl-9-oxo-                                                                         8β-methyl-9-oxo-15-hy-                                   11α,15-dihydro-                                                                         droxy-16,16-dimethyl-                                         xy-16,16-di-    5-cis,10,13-cis-pro-                                          methyl-5-cis,13-                                                                              statrienoic acid                                              cis-prostadie-                                                                noic acid (Exam-                                                              ple 1374)                                                             1474    8α-methyl-9-oxo-                                                                        8α-methyl-9-oxo-15-hy-                                  11α,15-dihydro-                                                                         droxy-16,16-dimethyl-                                         xy-16,16-di-    8-iso-5-cis,10,13-cis-                                        methyl-8-iso-5- prostatrienoic acid                                           cis,13-cis-pro-                                                               stadienoic acid                                                               (Example 1374)                                                        1475    8β-methyl-9-oxo-                                                                         8β-methyl-9-oxo-15-hy-                                   11α,15-dihydro-                                                                         droxy-4-nor-20-methyl-                                        xy-4-nor-20-    5-cis,10,13-trans-pro-                                        methyl-5-cis,-  statrienoic acid                                              13-trans-prosta-                                                              dienoic acid                                                                  (Example 1375)                                                        1476    8α-methyl-9-oxo-                                                                        8α-methyl-9-oxo-15-hy-                                  11α,15-dihydro-                                                                         droxy-4-nor-20-methyl-                                        xy-4-nor-20-    8-iso-5-cis,10,13-                                            methyl-8-iso-   trans-prostatrienoic                                          5-cis,13-trans- acid                                                          prostadienoic                                                                 acid (Example                                                                 1375)                                                                 1477    8β-methyl-9-oxo-                                                                         8β-methyl-9-oxo-15-hy-                                   11α,15-dihydro-                                                                         droxy-4-nor-20-methyl-                                        xy-4-nor-20-    5-cis,10,13-cis-pro-                                          methyl-5-cis,-  statrienoic acid                                              13-cis-prostadi-                                                              enoic acid                                                                    (Example 1375)                                                        1478    8α-methyl-9-oxo-                                                                        8α-methyl-9-oxo-15-hy-                                  11α,15-dihydro-                                                                         droxy-4-nor-20-methyl-                                        xy-4-nor-20-    8-iso-5-cis,10,13-                                            methyl-8-iso-   cis-prostatrienoic                                            5-cis,13-cis-   acid                                                          prostadienoic                                                                 acid (Example                                                                 1375)                                                                 1479    8β-methyl-9-oxo-                                                                         8β-methyl-9-oxo-15-hy-                                   11α,15-dihydro-                                                                         droxy-4a-homo-17,17-di-                                       xy-4a-homo-17,- methyl-5-cis,10,13-                                           17-dimethyl-5-  trans-prostatrienoic                                          cis,13-trans-   acid                                                          prostadienoic                                                                 acid (Example                                                                 1376)                                                                 1480    8α-methyl-9-oxo-                                                                        8α-methyl-9-oxo-15-hy-                                  11α,15-dihydro-                                                                         droxy-4a-homo-17,17-di-                                       xy-4a-homo-17,- methyl-8-iso-5-cis,10-                                        17-dimethyl-8-  13-trans-prostatrienoic                                       iso-5-cis,13-   acid                                                          trans-prostadi-                                                               enoic acid (Exam-                                                             ple 1376)                                                             1481    8β-methyl-9-oxo-                                                                         8β-methyl-9-oxo-15-hy-                                   11α,15-dihydro-                                                                         droxy-4a-homo-17,17-di-                                       xy-4a-homo-17,- methyl-5-cis,10,13-cis-                                       17-dimethyl-5-  prostatrienoic acid                                           cis,13-cis-pro-                                                               stadienoic acid                                                               (Example 1376)                                                        1482    8α-methyl-9-oxo-                                                                        8α-methyl-9-oxo-15-hy-                                  11α,15-dihydro-                                                                         droxy-4a-homo-17,17-di-                                       xy-4a-homo-17,- methyl-8-iso-5-cis,10-                                        17-dimethyl-8-  13-cis-prostatrienoic                                         iso-5-cis,13-   acid                                                          cis-prostadie-                                                                noic acid (Exam-                                                              ple 1376)                                                             1483    8β-methyl-9-oxo-                                                                         8β-methyl-9-oxo-15-hy-                                   11α,15-dihydro-                                                                         droxy-4a,4b-bishomo-                                          xy-4a,4b-bis-   20-ethyl-5-cis,10,13-                                         homo-20-ethyl-  trans-prostatrienoic                                          5-cis,13-trans- acid                                                          prostadienoic                                                                 acid (Example                                                                 1377)                                                                 1484    8α-methyl-9-oxo-                                                                        8α-methyl-9-oxo-15-hy-                                  11α,15-dihydro-                                                                         droxy-4a,4b-bishomo-                                          xy-4a,4b-bis-   20-ethyl-8-iso-5-cis,-                                        homo-20-ethyl-8-                                                                              10,13-trans-prostatrie-                                       iso-5-cis,13-   noic acid                                                     trans-prostadi-                                                               enoic acid                                                                    (Example 1377)                                                        1485    8β-methyl-9-oxo-                                                                         8β-methyl-9-oxo-15-hy-                                   11α,15-dihydro-                                                                         droxy-4a,4b-bishomo-                                          xy-4a,4b-bis-   20-ethyl-5-cis,10,13-                                         homo-20-ethyl-5-                                                                              cis-prostatrienoic                                            cis,13-cis-pro- acid                                                          stadienoic acid                                                               (Example 1377)                                                        1486    8α-methyl-9-oxo-                                                                        8α-methyl-9-oxo-15-hy-                                  11α,15-dihydro-                                                                         droxy-4a,4b-bishomo-                                          xy-4a,4b bishomo-                                                                             20-ethyl-8-iso-5-cis,-                                        20-ethyl-8-iso- 10,13-cis-prostatrie-                                         5-cis,13-cis-   noic acid                                                     prostadienoic                                                                 acid (Example                                                                 1377)                                                                 1487    8β-methyl-9-oxo-                                                                         8β-methyl-9-oxo-15-hy-                                   11α,15-dihydro-                                                                         droxy-4a,4b-bishomo-                                          xy-4a,4b-bishomo-                                                                             5-cis,10,13-trans,17-                                         5-cis,13-trans,-                                                                              cis-prostatetraenoic                                          17-cis-prostatri-                                                                             acid                                                          enoic acid                                                                    (Example 1378)                                                        1488    8α-methyl-9-oxo-                                                                        8α-methyl-9-oxo-15-hy-                                  11α,15-dihydro-                                                                         droxy-4a,4b-bishomo-                                          xy-4a,4b-bishomo-                                                                             8-iso-5-cis,10,13-                                            8-iso-5-cis,13- trans,17-cis-prostate-                                        trans,17-cis-   traenoic acid                                                 prostatrienoic                                                                acid (Example                                                                 1378)                                                                 1489    8β-methyl-9-oxo-                                                                         8β-methyl-9-oxo-15-hy-                                   11α,15-dihydro-                                                                         droxy-4a,4b-bishomo-5-                                        xy-4a,4b-bishomo-                                                                             cis,10,13-cis-17-cis-                                         5-cis,13-cis-   prostatetraenoic acid                                         17-cis-prosta-                                                                trienoic acid                                                                 (Example 1378)                                                        1490    8α-methyl-9-oxo-                                                                        8α-methyl-9-oxo-15-hy-                                  11α,15-dihydro-                                                                         droxy-4a,4b-bishomo-8-                                        xy-4a,4b-bishomo-                                                                             iso-5-cis,10,13-cis-                                          8-iso-5-cis,13- 17-cis-prostatetrae-                                          cis-17-cis-pro- noic acid                                                     statrienoic acid                                                              (Example 1378)                                                        1491    methyl 8β-methyl-                                                                        methyl 8β-methyl-9-oxo-                                  9-oxo-11α,15-di-                                                                        15-hydroxy-20-methyl-                                         hydroxy-20-methyl                                                                             10,13-trans-prostadi-                                         13-trans-proste-                                                                              enoate                                                        noate (Example                                                                1379)                                                                 1492    methyl 8α-methyl-                                                                       methyl 8α-methyl-9-oxo-                                 9-oxo-11α,15-di-                                                                        15-hydroxy-20-methyl-                                         hydroxy-20-     8-iso-10,13-trans-pro-                                        methyl-8-iso-   stadienoate                                                   13-trans-pro-                                                                 stenoate (Exam-                                                               ple 1379)                                                             1493    methyl 8β-methyl-                                                                        methyl 8β-methyl-9-oxo-                                  9-oxo-11α,15-di-                                                                        15-hydroxy-20-methyl-                                         hydroxy-20-     10,13-cis-prostadie-                                          methyl-13-cis-  noate                                                         prostenoate                                                                   (Example 1379)                                                        1494    methyl 8α-methyl-                                                                       methyl 8α methyl-9-oxo-                                 9-oxo-11α,15-di-                                                                        15-hydroxy-20-methyl-                                         hydroxy-20-     8-iso-10,13-cis-pro-                                          methyl-8-iso-   stadienoate                                                   13-cis-proste-                                                                noate (Example                                                                1379)                                                                 1495    ethyl 8β-methyl-                                                                         ethyl 8β-methyl-9-oxo-                                   9-oxo-11α,15-di-                                                                        15-hydroxy-7a,7b-bis-                                         hydroxy-7a,7b-  homo-10,13-trans,17-                                          bishomo-13-     cis-prostatrienoate                                           trans,17-cis-                                                                 prostadienoate                                                                (Example 1380)                                                        1496    ethyl 8α-methyl-                                                                        ethyl 8α-methyl-9-oxo-                                  9-oxo-11α,15-di-                                                                        15-hydroxy-7a,7b-bis-                                         hydroxy-7a,7b-  homo-8-iso-10,13-trans,-                                      bishomo-8-iso-  17-cis-prostatrienoate                                        13-trans,17-                                                                  cis-prostadie-                                                                noate (Example                                                                1380)                                                                 1497    ethyl 8β-methyl-                                                                         ethyl 8β-methyl-9-oxo-                                   9-oxo-11α,15-                                                                           15-hydroxy-7a,7b-bis-                                         dihydroxy-7a,-  homo-10,13-cis,17-cis-                                        7b-bishomo-13-  prostatrienoate                                               cis,17-cis-pro-                                                               stadienoate                                                                   (Example 1380)                                                        1498    ethyl 8α-methyl-                                                                        ethyl 8α-methyl-9-oxo-                                  9-oxo-11α,15-di-                                                                        15-hydroxy-7a,7b-bis-                                         hydroxy-7a,7b-  homo-8-iso-10,13-cis,-                                        bishomo-8-iso-  17-cis-prostatrienoate                                        13-cis,17-cis-                                                                prostadienoate                                                                (Example 1380)                                                        1499    ethyl 8β-methyl-                                                                         ethyl 8β-methyl-9-oxo-                                   9-oxo-11α,15-di-                                                                        15-hydroxy-2-ethyl-                                           hydroxy-2-ethyl-                                                                              16,16-dimethyl-10,13-                                         16,16-dimethyl- trans-prostadienoate                                          13-trans-proste-                                                              noate (Example                                                                1381)                                                                 1500    ethyl 8α-methyl-                                                                        ethyl 8α-methyl-9-oxo-                                  9-oxo-11α,15-di-                                                                        15-hydroxy-2-ethyl-                                           hydroxy-2-ethyl-                                                                              16,16-dimethyl-8-iso-                                         16,16-dimethyl- 10,13-trans-prostadi-                                         8-iso-13-trans- enoate                                                        prostenoate                                                                   (Example 1381)                                                        1501    ethyl 8β-methyl-                                                                         ethyl 8β-methyl-9-oxo-                                   9-oxo-11α,15-di-                                                                        15-hydroxy-2-ethyl-                                           hydroxy-2-ethyl-                                                                              16,16-dimethyl-10,13-                                         16,16-dimethyl- cis-prostadienoate                                            13-cis-proste-                                                                noate (Example                                                                1381)                                                                 1502    ethyl 8α-methyl-                                                                        ethyl 8α-methyl-9-oxo-                                  9-oxo-11α,15-di-                                                                        15-hydroxy-2-ethyl-                                           hydroxy-2-ethyl-                                                                              16,16-dimethyl-8-iso-                                         16,16-dimethyl- 10,13-cis-prostadie-                                          8-iso-13-cis-   noate                                                         prostenoate                                                                   (Example 1381)                                                        1503    ethyl 8β-methyl-                                                                         ethyl 8β-methyl-9-oxo-                                   9-oxo-11α,15-di-                                                                        15-hydroxy-3,3,17,17-                                         hydroxy-3,3,17,-                                                                              tetramethyl-10,13-                                            17-tetramethyl- trans-prostadienoate                                          13-trans-proste-                                                              noate (Example                                                                1382)                                                                 1504    ethyl 8α-methyl-                                                                        ethyl 8α-methyl-9-oxo-                                  9-oxo-11α,15-di-                                                                        15-hydroxy-3,3,17,17-                                         hydroxy-3,3,17,-                                                                              tetramethyl-8-iso-10,-                                        17-tetramethyl-8-                                                                             13-trans-prostadienoate                                       iso-13-trans-pro-                                                             stenoate (Example                                                             1382)                                                                 1505    ethyl 8β-methyl-                                                                         ethyl 8β-methyl-9-oxo-                                   9-oxo-11α,15-di-                                                                        15-hydroxy-3,3,17,17-                                         hydroxy-3,3,17,-                                                                              tetramethyl-10,13-cis-                                        17-tetramethyl- prostadienoate                                                13-cis-proste-                                                                noate (Example                                                                1382)                                                                 1506    ethyl 8α-methyl-                                                                        ethyl 8α-methyl-9-oxo-                                  9-oxo-11α,15-di-                                                                        15-hydroxy-3,3,17,17-                                         hydroxy-3,3,17,-                                                                              tetramethyl-8-iso-10,-                                        17-tetramethyl- 13-cis-prostadienoate                                         8-iso-13-cis-                                                                 prostenoate                                                                   (Example 1382)                                                        1507    ethyl 8β-methyl-                                                                         ethyl 8β-methyl-9-oxo-                                   9-oxo-11α,15-di-                                                                        15-hydroxy-3-oxa-17,-                                         hydroxy-3-oxa-  17-dimethyl-10,13-trans-                                      17,17-dimethyl- prostadienoate                                                13-trans-proste-                                                              noate (Example                                                                1383)                                                                 1508    ethyl 8α-methyl-                                                                        ethyl 8α-methyl-9-oxo-                                  9-oxo-11α,15-di-                                                                        15-hydroxy-3-oxa-17,17-                                       hydroxy-3-oxa-  dimethyl-8-iso-10,13-                                         17,17-dimethyl- trans-prostadienoate                                          8-iso-13-trans-                                                               prostenoate                                                                   (Example 1383)                                                        1509    ethyl 8β-methyl-                                                                         ethyl 8β-methyl-9-oxo-                                   9-oxo-11α,15-di-                                                                        15-hydroxy-3-oxa-17,17-                                       hydroxy-3-oxa-  dimethyl-10,13-cis-                                           17,17-dimethyl- prostadienoate                                                13-cis-proste-                                                                noate (Example                                                                1383)                                                                 1510    ethyl 8α-methyl-                                                                        ethyl 8α-methyl-9-oxo-                                  9-oxo-11α,15-di-                                                                        15-hydroxy-3-oxa-17,-                                         hydroxy-3-oxa-  17-dimethyl-8-iso-10,-                                        17,17-dimethyl- 13-cis-prostadienoate                                         8-iso-13-cis-                                                                 prostenoate                                                                   (Example 1383)                                                        1511    butyl 8β-methyl-                                                                         butyl 8β-methyl-9-oxo-                                   9-oxo-11α,15-di-                                                                        15-hydroxy-10,13-trans-                                       hydroxy-13-trans-                                                                             prostadienoate                                                prostenoate                                                                   (Example 1384)                                                        1512    butyl 8α-methyl-                                                                        butyl 8α-methyl-9-oxo-                                  9-oxo-11α,15-di-                                                                        15-hydroxy-8-iso-10,-                                         hydroxy-8-iso-13-                                                                             13-trans-prostadienoate                                       trans-prosteno-                                                               ate (Example                                                                  1384)                                                                 1513    butyl 8β-methyl-                                                                         butyl 8β-methyl-9-oxo-                                   9-oxo-11α,15-di-                                                                        15-hydroxy-13-cis-pro-                                        hydroxy-13-cis- stadienoate                                                   prostenoate                                                                   (Example 1384)                                                        1514    butyl 8α-methyl-                                                                        butyl 8α-methyl-9-oxo-                                  9-oxo-11α,15-di-                                                                        15-hydroxy-8-iso-10,13-                                       hydroxy-8-iso-13-                                                                             cis-prostadienoate                                            cis-prostenoate                                                               (Example 1384)                                                        1515    decyl 8β-methyl-                                                                         decyl 8β-methyl-9-oxo-                                   9-oxo-11α,15-di                                                                         15-hydroxy-10,13-trans,-                                      hydroxy-13-trans,-                                                                            17-cis-prostatrienoate                                        17-cis-prostadi-                                                              enoate (Example                                                               1385)                                                                 1516    decyl 8α-methyl-                                                                        decyl 8α-methyl-9-oxo-                                  9-oxo-11α,15-di-                                                                        15-hydroxy-8-iso-10,-                                         hydroxy-8-iso-  13-trans,17-cis-prosta-                                       13-trans,17-cis-                                                                              trienoate                                                     prostadienoate                                                                (Example 1385)                                                        1517    decyl 8β-methyl-                                                                         decyl 8β-methyl-9-oxo-                                   9-oxo-11α,15-di-                                                                        15-hydroxy-10,13-cis                                          hydroxy-13-cis- 17-cis-prostatrienoate                                        17-cis-prostadi-                                                              enoate (Example                                                               1385                                                                  1518    decyl 8α-methyl-                                                                        decyl 8α-methyl-9-oxo-                                  9-oxo-11α,15-di-                                                                        15-hydroxy-8-iso-10,13-                                       hydroxy-8-iso-13-                                                                             cis-17-cis-prostatrie-                                        cis-17-cis-pro- noate                                                         stadienoate                                                                   (Example 1385)                                                        1519    ethyl 8β-methyl-                                                                         ethyl 8β-methyl-9-oxo-                                   9-oxo-11α-ace-                                                                          15-hydroxy-10,13-trans-                                       toxy-15-hydroxy-                                                                              prostadienoate                                                13-trans-proste-                                                              noate (Example                                                                1386)                                                                 1520    ethyl 8α-methyl-                                                                        ethyl 8α-methyl-9-oxo-                                  9-oxo-11α-ace-                                                                          15-hydroxy-8-iso-10,13-                                       toxy-15-hydroxy-                                                                              trans-prostadienoate                                          8-iso-13-trans-                                                               prostenoate                                                                   (Example 1386)                                                        1521    ethyl 8β-methyl-                                                                         ethyl 8β-methyl-9-oxo-                                   9-oxo-11α-ace-                                                                          15-hydroxy-10,13-cis-                                         toxy-15-hydroxy-                                                                              prostadienoate                                                13-cis-proste-                                                                noate (Example                                                                1386)                                                                 1522    ethyl 8α-methyl-                                                                        ethyl 8α-methyl-9-oxo-                                  9-oxo-11α-ace-                                                                          15-hydroxy-8-iso-10,13-                                       toxy-15-hydroxy-                                                                              cis-prostadienoate                                            8-iso-13-cis-                                                                 prostenoate                                                                   (Example 1386)                                                        ______________________________________                                    

EXAMPLES 1523-1654

Treatment of the designated 9-oxo-prostenoic acid and ester derivativeslisted in Table 42 below with sodium borohydride in ethanol as describedin Example 257 gives the product 9α and 9β hydroxy derivatives of thetable, which are separable by standard chromatographic techniques.

                  TABLE 42                                                        ______________________________________                                                 Starting 8-     Product                                                       methyl-9-oxo-   8-methyl-9α/β,-                                    11α,15-di-                                                                              11α,15-trihydroxy-                             Ex-      hydroxy-13-prosten-                                                                           13-prostenoic                                        ample    oic acid or ester                                                                             acid or ester                                        ______________________________________                                        1523     8β-methyl-prosta-                                                                        8β-methyl-prosta-                                        glandin E.sub.1 glandin F.sub.1 α/F.sub.1 β                        (Example 1353)                                                       1524     8α-methyl-8-iso-                                                                        8α-methyl-8-iso-pros-                                   prostaglandin E.sub.1                                                                         taglandin F.sub.1 α/F.sub.1 β                      (Example 1353)                                                       1525     8β-methyl-9-oxo-11α-                                                               8β-methyl-9α/β,11α,                     15-dihydroxy-13-cis-                                                                          15-trihydroxy-13-                                             prostenoic acid cis-prostenoic acid                                           (Example 1353)                                                       1526     8α-methyl-9-oxo-                                                                        8α-methyl-9α/β, 11α,                   11α,15-dihydroxy-                                                                       15-trihydroxy-8-iso-                                          8-iso-13-cis-pros-                                                                            13-cis-prostenoic                                             tenoic acid     acid                                                          (Example 1353)                                                       1527     8β-methyl-9-oxo-                                                                         8β-methyl-9α/β,11α,-                    11α,15-dihydroxy-                                                                       15-trihydroxy-16,16-                                          16,16-dimethyl-13-                                                                            dimethyl-13-trans-                                            trans-prostenoic                                                                              prostenoic acid                                               acid                                                                          (Example 1354)                                                       1528     8α-methyl-9-oxo-                                                                        8α-methyl-9α/β,11α,-                   11α,15-dihydroxy-                                                                       15-trihydroxy-16,16-                                          16,16-dimethyl-8-                                                                             dimethyl-8-iso-13-                                            iso-13-trans-pros-                                                                            trans-prostenoic acid                                         tenoic acid                                                                   (Example 1354)                                                       1529     8β-methyl-9-oxo-                                                                         8β-methyl-9α/β,11α-                     11α,15-dihydroxy-                                                                       15-trihydroxy-16,16-                                          16,16-dimethyl-13-,                                                                           dimethyl-13-cis-                                              cis-prostenoic acid                                                                           prostenoic acid                                               (Example 1354)                                                       1530     8α-methyl-9-oxo-                                                                        8α-methyl-9α/β,11α,                    11α ,15-dihydroxy-                                                                      15-trihydroxy-16,16-                                          16,16-dimethyl-8-                                                                             dimethyl-8-iso-13-                                            iso-13-cis-pros-                                                                              cis-prostenoic acid                                           tenoic acid                                                                   (Example 1354)                                                       1531     8β-methyl-9-oxo-11α-                                                               8β-methyl-9α/β,11α,-                    15-dihydroxy-17,17-                                                                           15-trihydroxy-17,17-                                          dimethyl-13-trans-                                                                            dimethyl-13-trans-                                            prostenoic acid prostenoic acid                                               (Example 1355)                                                       1532     8α-methyl-9-oxo-                                                                        8α-methyl-9α/β,11α,-                   11α,15-dihydroxy-8-                                                                     15-trihydroxy-17,17-                                          iso-17,17-di-   dimethyl-8-iso-13-                                            methyl-13-trans-                                                                              trans-prostenoic                                              prostenoic acid acid                                                          (Example 1355)                                                       1533     8β-methyl-9-oxo-                                                                         8β-methyl-9α/β,11α,-                    11α,15-dihydroxy-17,                                                                    15-trihydroxy-17,17-                                          17-dimethyl-13-cis-                                                                           dimethyl-13-cis-                                              prostenoic acid prostenoic acid                                               (Example 1355)                                                       1534     8α-methyl-9-oxo-                                                                        8α-methyl-9α/β,11α,-                   11α,15-dihydroxy-                                                                       15-trihydroxy-8-iso-                                          17,17-dimethyl-8-                                                                             17,17-dimethyl-13-                                            iso-13-cis-pros-                                                                              cis-prostenoic                                                tenoic acid     acid                                                          (Example 1355)                                                       1535     8β-methyl-9-oxo-11α-                                                               8β-methyl-9α/β,11α-                     15-dihydroxy-13-                                                                              15-trihydroxy-13-                                             trans-17-cis-pro-                                                                             trans,17-cis-pros-                                            stadienoic acid tadienoic acid                                                (Example 1356)                                                       1536     8α-methyl-9-oxo-11α-                                                              8α-methyl-9α/β,11α,-                   15-dihydroxy-8-iso-                                                                           15-trihydroxy-8-iso-                                          13-trans,17-cis-                                                                              13-trans-17-cis-                                              prostadienoic acid                                                                            prostadienoic acid                                            (Example 1356)                                                       1537     8β-methyl-9-oxo-11α-                                                               8β-methyl-9α/β,11α,-                    15-dihydroxy-13-cis,                                                                          15-trihydroxy-13-cis,                                         17-cis-prostadienoic                                                                          17-cis-prostadienoic                                          acid            acid                                                          (Example 1356)                                                       1538     8α-methyl-9-oxo-11α-                                                              8α-methyl-9α/β,11α,-                   15-dihydroxy-8-iso-                                                                           15-trihydroxy-8-iso-                                          13-trans-17-cis-                                                                              13-cis,17-cis-pros-                                           prostadienoic acid                                                                            tadienoic acid                                                (Example 1356)                                                       1539     8β-methyl-9-oxo-11α-                                                               8β-methyl-9α/β,11α,-                    15-dihydroxy-20-                                                                              15-trihydroxy-20-                                             ethyl-13-trans-pros-                                                                          ethyl-13-trans-pros-                                          tenoic acid     tenoic acid                                                   (Example 1357)                                                       1540     8α-methyl-9-oxo-11α-                                                              8α-methyl-9α/β,11α,                    15-dihydroxy-20-                                                                              15-trihydroxy-20-                                             ethyl-8-iso-13-trans-                                                                         ethyl-8-iso-13-                                               prostenoic acid trans-prostenoic                                              (Example 1357)  acid                                                 1541     8β-methyl-9-oxo-11α-                                                               8β-methyl-9α/β,11α,-                    15-dihydroxy-20-eth-                                                                          15-trihydroxy-20-                                             yl-13-cis-prostenoic                                                                          ethyl-13-cis-pro-                                             acid            stenoic acid                                                  (Example 1357)                                                       1542     8α-methyl-9-oxo-11α-                                                              8α-methyl-9α/β,11α,-                   15-dihydroxy-20-                                                                              15-trihydroxy-20-                                             ethyl-8-iso-13-cis-                                                                           ethyl-8-iso-13-cis-                                           prostenoic acid prostenoic acid                                               (Example 1357)                                                       1543     8β-methyl-9-oxo-11α,-                                                              8β-methyl-9α/β,11α,-                    15-dihydroxy-6,7-                                                                             15-trihydroxy-6,7-                                            dinor-13-trans-pros-                                                                          dinor-13-trans-pros-                                          tenoic acid     tenoic acid                                                   (Example 1358)                                                       1544     8α-methyl-9-oxo-11α,-                                                             8α-methyl-9α/β,11α,-                   15-dihydroxy-6,7-                                                                             15-trihydroxy-6,7-                                            dinor-8-iso-13-trans-                                                                         dinor-8-iso-13-                                               prostenoic acid trans-prostenoic                                              (Example 1358)  acid                                                 1545     8β-methyl-9-oxo-11α,-                                                              8β-methyl-9α/β,11α,-                    15-dihydroxy-6,7-                                                                             15-trihydroxy-6,7-                                            dinor-13-cis-   dinor-13-cis-                                                 prostenoic acid prostenoic acid                                               (Example 1358)                                                       1546     8α-methyl-9-oxo-11α,-                                                             8α-methyl-9α/β,11α,-                   15-dihydroxy-6,7-                                                                             15-trihydroxy-6,7-                                            dinor-8-iso-13-cis-                                                                           dinor-8-iso-13-cis-                                           prostenoic acid prostenoic acid                                               (Example 1358)                                                       1547     8β-methyl-9-oxo-11α,-                                                              8β-methyl-9α/β,11α,-                    15-dihydroxy-5,6,7-                                                                           15-trihydroxy-5,6,7-                                          trinor-20-methyl-13-                                                                          trinor-20-methyl-13-                                          trans-prostenoic acid                                                                         trans-prostenoic acid                                         (Example 1359)                                                       1548     8α-methyl-9-oxo-11α,-                                                             8α-methyl-9α/β,11α,-                   15-dihydroxy-5,6,7-                                                                           15-trihydroxy-5,6,7-                                          trinor-20-methyl-8-                                                                           trinor-20-methyl-8-                                           iso-13-trans-pros-                                                                            iso-13-trans-prosten-                                         tenoic acid     oic acid                                                      (Example 1359)                                                       1549     8β-methyl-9-oxo-11α-                                                               8β-methyl-9α/β,11α,-                    15-dihydroxy-5,6,7-                                                                           15-trihydroxy-5,6,7-                                          trinor-20-methyl-                                                                             trinor-20-methyl-13-                                          13-cis-prostenoic                                                                             cis-prostenoic acid                                           acid                                                                          (Example 1359)                                                       1550     8α-methyl-9-oxo-11α,-                                                             8α-methyl-9α/β,11α,-                   15-dihydroxy-5,6,7-                                                                           15-trihydroxy-5,6,7-                                          trinor-20-methyl-8-                                                                           trinor-20-methyl-8-                                           iso-13-cis-prosten-                                                                           iso-13-cis-prosten-                                           oic acid        oic acid                                                      (Example 1359)                                                       1551     8β-methyl-9-oxo-11α,-                                                              8β-methyl-9α/β,11α,-                    15-dihydroxy-7a,7b-                                                                           15-trihydroxy-7a,7b-                                          bishomo-13-trans-                                                                             bishomo-13-trans-                                             prostenoic acid prostenoic acid                                               (Example 1360)                                                       1552     8α-methyl-9-oxo-11α,-                                                             8α-methyl-9α/β,11α,-                   15-dihydroxy-7a,7b-                                                                           15-trihydroxy-7a,7b-                                          bishomo-8-iso-13-                                                                             bishomo-8-iso-13-                                             trans-prostenoic                                                                              trans prostenoic                                              acid            acid                                                          (Example 1360)                                                       1553     8β-methyl-9-oxo-11α,-                                                              8β-methyl-9α/β,11α,                     15-dihydroxy-7a,7b-                                                                           15-trihydroxy-7a,7b-                                          bishomo-13-cis- bishomo-13-cis-pro-                                           prostenoic acid stenoic acid                                                  (Example 1360)                                                       1554     8α-methyl-9-oxo-11α,-                                                             8α-methyl-9α/β,11α,-                   15-dihydroxy-7a,7b-                                                                           15-trihydroxy-7a,7b-                                          bishomo-8-iso-13-                                                                             bishomo-8-iso-13-cis-                                         cis-prostenoic acid                                                                           prostenoic acid                                               (Example 1360)                                                       1555     8β-methyl-9-oxo-11α,-                                                              8β-methyl-9α/β,11α,-                    15-dihydroxy-2-eth-                                                                           15-trihydroxy-2-                                              yl-13-trans-prosten-                                                                          ethyl-13-trans-                                               oic acid        prostenoic acid                                               (Example 1361)                                                       1556     8α-methyl-9-oxo-11α,-                                                             8α-methyl-9α/β,11α,-                   15-dihydroxy-2-eth-                                                                           15-trihydroxy-2-                                              yl-8-iso-13-trans-                                                                            ethyl-8-iso-13-trans-                                         prostenoic acid prostenoic acid                                               (Example 1361)                                                       1557     8β-methyl-9-oxo-11α,-                                                              8β-methyl-9α/β,11α,-                    15-dihydroxy-2-ethyl-                                                                         15-trihydroxy-2-                                              13-cis-prostenoic                                                                             ethyl-13-cis-pro-                                             acid            stenoic acid                                                  (Example 1361)                                                       1558     8α-methyl-9-oxo-11α,-                                                             8α-methyl-9α/β,11α-                    15-dihydroxy-2- 15,trihydroxy-2-                                              ethyl-8-iso-13-cis-                                                                           ethyl-8-iso-13-cis-                                           prostenoic acid prostenoic acid                                               (Example 1361)                                                       1559     8β-methyl-9-oxo-11α,-                                                              8β-methyl-9α/β,11α,-                    15-dihydroxy-3,3,20-                                                                          15-trihydroxy-3,3,20-                                         trimethyl-8-iso-13-                                                                           trimethyl-13-trans-                                           trans-prostenoic                                                                              prostenoic acid                                               acid (Example 1362)                                                  1560     8α-methyl-9-oxo-11α,-                                                             8β-methyl-9α/β,11α,-                    15-dihydroxy-3,3,20-                                                                          15-trihydroxy-3,3,                                            trimethyl-8-iso-13-                                                                           20-trimethyl-8-iso-                                           trans-prostenoic ac                                                                           13-trans-prostenoic                                           acid (Example 1362)                                                                           acid                                                 1561     8β-methyl-9-oxo-11α,-                                                              8β-methyl-9α/β,11α,-                    15-dihydroxy-3,3,20-                                                                          15-trihydroxy-3,3,                                            trimethyl-13-cis-                                                                             20-trimethyl-13-cis-                                          prostenoic acid prostenoic acid                                               (Example 1362)                                                       1562     8α-methyl-9-oxo-11α,-                                                             8α-methyl-9α/β,11α,-                   15-dihydroxy-3,3,20-                                                                          15-trihydroxy-3,3,20-                                         trimethyl-8-iso-13-                                                                           trimethyl-8-iso-13-                                           cis-prostenoic acid                                                                           cis-prostenoic acid                                           (Example 1362)                                                       1563     8β-methyl-9-oxo-11α,-                                                              8β-methyl-9α/β,11α,-                    15-dihydroxy-3-oxa-                                                                           15-trihydroxy-3-oxa-                                          13-trans-prostenoic                                                                           13-trans-prostenoic                                           acid            acid                                                          (Example 1363)                                                       1564     8α-methyl-9-oxo-11α,-                                                             8α-methyl-9α/β,11α,-                   15-dihydroxy-3-oxa-                                                                           15-trihydroxy-3-oxa-                                          8-iso-13-trans- 8-iso-13-trans-                                               prostenoic acid prostenoic acid                                               (Example 1363)                                                       1565     8β-methyl-9-oxo-11α,-                                                              8β-methyl-9α/β,11α,-                    15-dihydroxy-3-oxa-8                                                                          15-trihydroxy-3-oxa-                                          8-iso-13-pro-   8-iso-13-cis-pro-                                             stenoic acid    stenoic acid                                                  (Example 1363)                                                       1566     8α-methyl-9-oxo-11α,-                                                             8α-methyl-9α/β,11α,-                   15-dihydroxy-3-oxa-                                                                           15-trihydroxy-3-oxa-                                          8-iso-13-cis-pro-                                                                             8-iso-13-cis-pro-                                             stenoic acid    stenoic acid                                                  (Example 1363)                                                       1567     8β-methyl-9-oxo-11α,-                                                              8β-methyl-9α/β-11α,-                    15-dihydroxy-3-oxa-                                                                           15-trihydroxy-3-oxa-                                          16,16-dimethyl-13-                                                                            16,16-dimethyl-13-                                            trans-prostenoic                                                                              trans-prostenoic                                              acid            acid                                                          (Example 1364)                                                       1568     8α-methyl-9-oxo-11α,-                                                             8α-methyl-9α/β-11α,-                   15-dihydroxy-3-oxa-                                                                           5-trihydroxy-3-oxa-                                           16,16-dimethyl-8-                                                                             16,16-dimethyl-8-                                             iso-13-trans-pro-                                                                             iso-13-trans-pro-                                             stenoic acid    stenoic acid                                                  (Example 1364)                                                       1569     8β-methyl-9-oxo-11α,-                                                              8β-methyl-9α/β-11α,-                    15-dihydroxy-3-oxa-                                                                           15-trihydroxy-3-oxa-                                          16,16-dimethyl-13-                                                                            16,16-dimethyl-13-                                            cis-prostenoic acid                                                                           cis-prostenoic acid                                           (Example 1364)                                                       1570     8α-methyl-9-oxo-11α,-                                                             8α-methyl-9α/β-11α,-                   15-dihydroxy-3-oxa-                                                                           15-trihydroxy-3-oxa-                                          16,16-dimethyl-8-                                                                             16,16-dimethyl-8-                                             iso-13-cis-pro- iso-13-cis-pro-                                               stenoic acid    stenoic acid                                                  (Example 1364)                                                       1571     8β-methyl-9-oxo-11α,-                                                              8β-methyl-9α/β,11α,-                    15-dihydroxy-3-oxa-                                                                           15-trihydroxy-3-oxa-                                          13-trans,17-cis-                                                                              13-trans,17-cis-                                              prostadienoic acid                                                                            prostadienoic acid                                            (Example 1365)                                                       1572     8α-methyl-9-oxo-11α,-                                                             8α-methyl-9α/β,11α,-                   15-dihydroxy-3-oxa-                                                                           15-trihydroxy-3-oxa-                                          8-iso-13-trans,17-                                                                            8-iso-13-trans,17-                                            cis-prostadienoic                                                                             cis-prostadienoic                                             acid            acid                                                          (Example 1365)                                                       1573     8β-methyl-9-oxo-11α,-                                                              8β-methyl-9α /β,11α,-                   15-dihydroxy-3-oxa-                                                                           15-trihydroxy-3-oxa-                                          13-cis,17-cis-pro-                                                                            13-cis,17-cis-                                                stadienoic acid prostadienoic acid                                            (Example 1365)                                                       1574     8α-methyl-9-oxo-11α,-                                                             8α-methyl-9α/β,11α,-                   15-dihydroxy-3-oxa-                                                                           15-trihydroxy-3-oxa-                                          8-iso-13-cis,17-cis-                                                                          8-iso-13-cis,17-cis-                                          prostadienoic acid                                                                            prostadienoic acid                                            (Example 1365)                                                       1575     8β-methyl-9-oxo-11α,-                                                              8β-methyl-9α/β,11α,-                    15-dihydroxy-3-oxa-                                                                           15-trihydroxy-3-oxa-                                          20-ethyl-13-trans-                                                                            20-ethyl-13-trans-                                            prostenoic acid prostenoic acid                                               (Example 1366)                                                       1576     8α-methyl-9-oxo-11α,-                                                             8α-methyl-9α/β,11α,-                   15-dihydroxy-3-oxa-                                                                           15-trihydroxy-3-oxa-                                          20-ethyl-8-iso-13-                                                                            20-ethyl-8-iso-13-                                            trans-prostenoic                                                                              trans-prostenoic                                              acid            acid                                                          (Example 1366)                                                       1577     8β-methyl-9-oxo-11α,-                                                              8β-methyl-9α/β,11α,-                    15-dihydroxy-3-oxa-                                                                           15-trihydroxy-3-oxa-                                          20-ethyl-13-cis-                                                                              20-ethyl-13-cis-                                              prostenoic acid prostenoic acid                                               (Example 1366)                                                       1578     8α-methyl-9-oxo-11α,-                                                             8α-methyl-9α/β,11α,-                   15-dihydroxy-3-oxa-                                                                           15-trihydroxy-3-oxa-                                          20-ethyl-8-iso-13-                                                                            20-ethyl-8-iso-13-                                            cis-prostenoic acid                                                                           cis-prostenoic acid                                           (Example 1366)                                                       1579     8β-methyl-9-oxo-11α,-                                                              8β-methyl-9α/β,11α,-                    15-dihydroxy-2-flu-                                                                           15-trihydroxy-2-                                              oro-17,17-dimethyl-                                                                           fluoro-17,17-dimeth-                                          13-trans-prostenoic                                                                           yl-13-trans-prosten-                                          acid            oic acid                                                      (Example 1367)                                                       1580     8α-methyl-9-oxo-11α,-                                                             8α-methyl-9α/β,11α,-                   15-dihydroxy-2-flu-                                                                           15-trihydroxy-2-                                              oro-17,17-dimethyl-                                                                           fluoro-17,17-dimeth-                                          8-iso-13-trans- yl-8-iso-13-trans-                                            prostenoic acid prostenoic acid                                               (Example 1367)                                                       1581     8β-methyl-9-oxo-11α,-                                                              8β-methyl-9α/β,11α,-                    15-dihydroxy-2- 15-trihydroxy-2-                                              fluoro-17,17-di-                                                                              fluoro-17,17-dimeth-                                          methyl-13-cis-pros-                                                                           yl-13-cis-prostenoic                                          tenoic acid     acid                                                          (Example 1367)                                                       1582     8α-methyl-9-oxo-11α,-                                                             8α-methyl-9α/β,11α,-                   15-dihydroxy-2-flu-                                                                           15-trihydroxy-2-                                              oro-17,17-dimethyl-                                                                           fluoro-17,17-dimeth-                                          8-iso-13-cis-pros-                                                                            yl-8-iso-13-cis-                                              tenoic acid     prostenoic acid                                               (Example 1367)                                                       1583     8β-methyl-9-oxo-11α,-                                                              8β-methyl-9α/β,11α,-                    15-dihydroxy-7-nor-                                                                           15-trihydroxy-7-nor-                                          13-trans-prostenoic                                                                           13-trans-prostenoic                                           acid            acid                                                          (Example 1368)                                                       1584     8α-methyl-9-oxo-11α,-                                                             8α-methyl-9α/β,11α,-                   15-dihydroxy-7-nor-                                                                           15-trihydroxy-7-nor-                                          8-iso-13-trans-pros-                                                                          8-iso-13-trans-pros-                                          tenoic acid     tenoic acid                                                   (Example 1368)                                                       1585     8β-methyl-9-oxo-11α,-                                                              8β-methyl-9α/β,11α,-                    15-dihydroxy-7-nor-                                                                           15-trihydroxy-7-nor-                                          13-cis-prostenoic                                                                             13-cis-prostenoic                                             acid            acid                                                          (Example 1368)                                                       1586     8α-methyl-9-oxo-11α,-                                                             8α-methyl-9α/β,11α,-                   15-dihydroxy-7-nor-                                                                           15-trihydroxy-7-nor-                                          8-iso-13-cis-prosten-                                                8-iso-13-cis-pro-                                                                      oic acid        stenoic acid                                                  (Example 1368)                                                       1587     8β-methyl-9-oxo-11α,-                                                              8β-methyl-9α/β,11α,-                    15-dihydroxy-7a-homo-                                                                         15-trihydroxy-7a-                                             16,16-dimethyl-13-                                                                            homo-16,16-dimethyl-                                          trans-prostenoic                                                                              13-trans-prostenoic                                           acid            acid                                                          (Example 1369)                                                       1588     8α-methyl-9-oxo-11α,-                                                             8α-methyl-9α/β,11α,-                   15-dihydroxy-7a-                                                                              15-trihydroxy-7a-                                             homo-16,16-dimethyl-                                                                          homo-16,16-dimethyl-                                          8-iso-13-trans-pros-                                                                          8-iso-13-trans-pro-                                           tenoic acid     stenoic acid                                                  (Example 1369)                                                       1589     8β-methyl-9-oxo-11α,-                                                              8β-methyl-9α/β,11α,-                    15-dihydroxy-7a-                                                                              15-trihydroxy-7a-                                             homo-16,16-dimethyl-                                                                          homo-16,16-dimethyl-                                          13-cis-prostenoic                                                                             13-cis-prostenoic                                             acid            acid                                                          (Example 1369)                                                       1590     8α-methyl-9-oxo-11α ,-                                                            8α-methyl-9α/β,11α,-                   15-dihydroxy-7a-                                                                              15-trihydroxy-7a-                                             homo-16,16-dimethyl-                                                                          homo-16,16-dimethyl-                                          8-iso-13-cis-prosten-                                                                         8-iso-13-cis-pros-                                            oic acid        tenoic acid                                                   (Example 1369)                                                       1591     8β-methyl-9-oxo-11α,-                                                              8β-methyl-9α/β,11α,-                    15-dihydroxy-2-phen-                                                                          15-trihydroxy-2-                                              yl-13-trans-prosten-                                                                          phenyl-13-trans-pros-                                         oic acid        tenoic acid                                                   (Example 1370)                                                       1592     8α-methyl-9-oxo-11α,-                                                             8α-methyl-9α/β,11α,-                   15-dihydroxy-2-phen-                                                                          15-trihydroxy-2-phen-                                         yl-8-iso-13-trans-                                                                            yl-8-iso-13-trans-                                            prostenoic acid prostenoic acid                                               (Example 1370)                                                       1593     8β-methyl-9-oxo-11α,-                                                              8β-methyl-9α/β,11α,-                    15-dihydroxy-2-phen-                                                                          15-trihydroxy-2-phen-                                         yl-13-cis-prostenoic                                                                          yl-13-cis-prostenoic                                          acid            acid                                                          (Example 1370)                                                       1594     8α-methyl-9-oxo-11α,-                                                             8α-methyl-9α/β,11α,-                   15-dihydroxy-2-phen-                                                                          15-trihydroxy-2-                                              yl-8-iso-13-cis-                                                                              phenyl-8-iso-13-cis-                                          prostenoic acid prostenoic acid                                               (Example 1370)                                                       1595     8β-methyl-9-oxo-11α,-                                                              8β-methyl-9α/β,11α,-                    15-dihydroxy-2-meth-                                                                          15-trihydroxy-2-meth-                                         yl-13-trans-17-cis-                                                                           yl-13-trans,17-cis-                                           prostadienoic acid                                                                            prostadienoic acid                                            (Example 1371)                                                       1596     8α-methyl-9-oxo-11α,-                                                             8α-methyl-9α/β,11α--                   15-dihydroxy-2- 15-trihydroxy-2-meth-                                         methyl-8-iso-13-                                                                              yl-8-iso-13                                                   trans,17-cis-prosta-                                                                          cis-                                                          dienoic acid    acid                                                          (Example 1371)                                                       1597     8β-methyl-9-oxo-11α,-                                                              8β-methyl-9α/β,11α,-                    15-dihydroxy-2-meth-                                                                          15-trihydroxy-2-                                              yl-13-cis,17-cis-                                                                             methyl-13-cis,17-cis-                                         prostadienoic acid                                                                            prostadienoic acid                                            (Example 1371)                                                       1598     8α-methyl-9-oxo-11α,-                                                             8α-methyl-9α/β,11α,-                   15-dihydroxy-2- 15-trihydroxy-2-meth-                                         methyl-8-iso-13-cis,                                                                          yl-8-iso-13-cis,17-                                           17-cis-prostadienoic                                                                          cis-prostadienoic                                             acid (Example 1371)                                                                           acid                                                 1599     8β-methyl-9-oxo-11α,-                                                              8β-methyl-9α/β,11α,-                    15-dihydroxy-5,cis,-                                                                          15-trihydroxy-5 cis-                                          13-trans-prosta-                                                                              13-trans-prostadien-                                          dienoic acid    oic acid                                                      (Example 1372)                                                       1600     8α-methyl-9-oxo-11α,-                                                             8α-methyl-9α/β,11α,-                   15-dihydroxy-8-iso-                                                                           15-trihydroxy-8-iso-                                          5-cis-13-trans-pros-                                                                          5 cis,13-trans-pros-                                          tadienoic acid  tadienoic acid                                                (Example 1372)                                                       1601     8β-methyl-9-oxo-11α,-                                                              8β-methyl-9α/β,11α,-                    15-dihydroxy-5-cis,                                                                           15-trihydroxy-5 cis-                                          13-cis-prostadien-                                                                            13-cis-prostadienoic                                          oic acid        acid                                                          (Example 1372)                                                       1602     8α-methyl-9-oxo-11α,-                                                             8α-methyl-9α/β,11α,-                   15-dihydroxy-8-iso-                                                                           15-trihydroxy-8-iso-                                          5-cis-13-cis-prosta-                                                                          5 cis 13-cis-prosta-                                          dienoic acid    dienoic acid                                                  (Example 1372)                                                       1603     8β-methyl-9-oxo-11α,-                                                              8β-methyl-9α/β,11α,-                    15-dihydroxy-5-cis,-                                                                          15-trihydroxy-5-cis,-                                         13-trans,17-cis-                                                                              13-trans,17-cis-                                              prostatrienoic acid                                                           (Example 1373)                                                       1604     8α-methyl-9-oxo-11α,-                                                             8α-methyl-9α/β,11α,-                   15-dihydroxy-8-iso-                                                                           15-dihydroxy-8-iso-                                           5-cis,13-trans,17-                                                                            5-cis,13-trans,17-                                            cis-prostatrienoic                                                                            cis-prostatrienoic                                            acid            acid                                                          (Example 1373)                                                       1605     8β-methyl-9-oxo-11α,-                                                              8β-methyl-9α/β,11α,-                    15-dihydroxy-5-cis,-                                                                          15-trihydroxy-5-cis,-                                         13-cis,17-cis-prosta-                                                                         13-cis,17-cis-                                                trienoic acid   prostatrienoic acid                                           (Example 1373)                                                       1606     8α-methyl-9-oxo-11α,-                                                             8α-methyl-9α/β,11α,-                   15-dihydroxy-8-iso-                                                                           15-trihydroxy-8-iso-                                          5-cis,13-cis,17-                                                                              5-cis,13-cis,17-cis-                                          cis-prostatrienoic                                                                            prostatrienoic acid                                           acid                                                                          (Example 1373)                                                       1607     8β-metyl-9-oxo-11α,-                                                               8β-methyl-9α /β,11α,-                   15-dihydroxy-16,16-                                                                           15-trihydroxy-16,16-                                          dimethyl-5-cis,13-                                                                            dimethyl-5-cis,13-                                            trans-prostadienoic                                                                           trans-prostadienoic                                           (Example 1374)  acid                                                 1608     8α-methyl-9-oxo-11α,-                                                             8α-methyl-9α/β,11α,-                   15-dihydroxy-16,16-                                                                           15-trihydroxy-16,16-                                          dimethyl-8-iso-5-                                                                             dimethyl-8-iso-5-cis-                                         cis,13-trans-prosta-                                                                          13-trans-prostadien-                                          dienoic acid    oic acid                                                      (Example 1374)                                                       1609     8β-methyl-9-oxo-11α,-                                                              8β-methyl-9α/β,11α,-                    15-dihydroxy-16,16-                                                                           15-trihydroxy-16,16-                                          dimethyl-5-cis  dimethyl-5-cis,13-                                            13-cis-prostadienoic                                                                          cis-prostadienoic                                             acid            acid                                                          (Example 1374)                                                       1610     8α-methyl-9-oxo-11α,-                                                             8α-methyl-9α/β,11α,-                   15-dihydroxy-16,16-                                                                           15-trihydroxy-16,16-                                          dimethyl-8-iso-5-cis-                                                                         dimethyl-8-iso-5-cis-                                         13-cis-prostadienoic                                                                          13-cis-prostadienoic                                          acid (Example 1374)                                                                           acid                                                 1611     8β-methyl-9-oxo-11α,-                                                              8β-methyl-9α/β,11α,-                    15-dihydroxy-4-nor-                                                                           15-trihydroxy-4-nor-                                          20-methyl-5-cis,13-                                                                           20-methyl-5-cis,13-                                           trans-prostadienoic                                                                           trans-prostadienoic                                           acid            acid                                                          (Example 1375)                                                       1612     8α-methyl-9-oxo-11α,-                                                             8α-methyl-9α/β,11α,-                   15-dihydroxy-4-nor-                                                                           15-trihydroxy-4-nor-                                          20-methyl-8-iso-5-                                                                            20-metyl-8-iso-                                               cis,13-trans-pros-                                                                            5-cis,13-trans-                                               tadienoic acid  prostadienoic acid                                            (Example 1375)                                                       1613     8β-methyl-9-oxo-11α,-                                                              8β-methyl-9α/β,11α,-                    15-dihydroxy-4-nor-                                                                           15-trihydroxy-4-nor-                                          20-methyl-5-cis,13-                                                                           20-methyl-5-cis,13-                                           cis-prostadienoic                                                                             cis-prostadienoic                                             acid            acid                                                          (Example 1375)                                                       1614     8α-methyl-9-oxo-11α,-                                                             8α-methyl-9α/β,11α,-                   15-dihydroxy-4-nor-                                                                           15-trihydroxy-4-nor-                                          20-methyl-8-iso-5-                                                                            20-methyl-8-iso-5-                                            cis,13-cis-prosta-                                                                            cis,13-cis-prosta-                                            dienoic acid    dienoic acid                                                  (Example 1375)                                                       1615     8β-methyl-9-oxo-11α,-                                                              8β-methyl-9α/β,11α,-                    15-dihydroxy-4a-homo-                                                                         15-trihydroxy-4a-                                             17,17-dimethyl-5-cis,                                                                         homo-17,17-dimethyl-                                          13-trans-prostadien-                                                                          5-cis,13-trans-pros-                                          oic acid        tadienoic acid                                                (Example 1376)                                                       1616     8α-methyl-9-oxo-11α,-                                                             8α-methyl-9α/β,11α,-                   15-dihydroxy-4a-homo-                                                                         15-trihydroxy-4a-                                             17,17-dimethyl-8-                                                                             homo-17,17-dimethyl-                                          iso-5-cis,13-trans-                                                                           8-iso-5-cis,13-cis-                                           prostadienoic acid                                                                            prostadienoic acid                                            (Example 1376)                                                       1617     8β-methyl-9-oxo-11α,-                                                              8β-methyl-9α/β,11α,-                    15-dihydroxy-4a-homo-                                                                         15-trihydroxy-4a-                                             17,17-dimethyl-5-cis-                                                                         homo-17,17-dimethyl-                                          13-cis-prostadienoic                                                                          5-cis,13-cis-prosta-                                          acid            dienoic acid                                                  (Example 1376)                                                       1618     8α-methyl-9-oxo-11α,-                                                             8α-methyl-9α/β,11α,-                   15-dihydroxy-4a-homo-                                                                         15-trihydroxy-4a-                                             17,17-dimethyl-8-iso-                                                                         homo-17,17-dimethyl-                                          5-cis,13-cis-prosta-                                                                          3-iso-5-cis,13-cis-                                           dienoic acid    prostadienoic acid                                            (Example 1376)                                                       1619     8β-methyl-9-oxo-11α,-                                                              8β-methyl-9α/β,11α,-                    15-dihydroxy-4a,4b-                                                                           15-trihydroxy-4a,4b-                                          bishomo-20-ethyl-5-                                                                           bishomo-20-ethyl-                                             cis,13-trans-prosta-                                                                          5-cis,13-trans-pros-                                          dienoic acid    tadienoic acid                                                (Example 1377)                                                       1620     8α-methyl-9-oxo-11α,-                                                             8α-methyl-9α/β,11α,-                   15-dihydroxy-4a,4b-                                                                           15-trihydroxy-4a,4b-                                          bishomo-20-ethyl-8-                                                                           bishomo-20-ethyl-8-                                           iso-5-cis,13-trans-                                                                           iso-5-cis,13-trans-                                           prostadienoic acid                                                                            prostadienoic acid                                            (Example 1377)                                                       1621     8β-methyl-9-oxo-11α,-                                                              8β-methyl-9α/β,11α,-                    15-dihydroxy-4a,4b-                                                                           15-trihydroxy-4a,4b-                                          bishomo-20-ethyl-5-                                                                           bishomo-20-ethyl-5-                                           cis,13-cis-prosta-                                                                            cis,13-cis-prosta-                                            dienoic acid    dienoic acid                                                  (Example 1377)                                                       1622     8α-methyl-9-oxo-11α,-                                                             8α-methyl-9α/β,11α,-                   15-dihydroxy-4a,4b-                                                                           15-trihydroxy-4a,4b-                                          bishomo-20-ethyl-8-                                                                           bishomo-20-ethyl-8-                                           iso-5-cis,13-cis-                                                                             iso-5-cis,13-cis-                                             prostadienoic acid                                                                            prostadienoic                                                 (Example 1377)                                                       1623     8β-methyl-9-oxo-11α  ,-                                                            8β-methyl-9α/β,11α,-                    15-dihydroxy-4a,4b-                                                                           15-trihydroxy-4a,4b-                                          bis-homo-5-cis,13-                                                                            bishomo-5-cis,13-                                             trans,17-cis-prosta-                                                                          trans,17-cis-prosta-                                          trienoic acid   trienoic acid                                                 (Example 1378)                                                       1624     8α-methyl-9-oxo-11α,-                                                             8α-methyl-9α/β,11α,-                   15-dihydroxy-4a,4b-                                                                           15-trihydroxy-4a,4b-                                          bis-homo-8-iso-5-cis-                                                                         bis-homo-8-iso-5-cis,-                                        13-trans,17-cis-pros-                                                                         13-trans,17-cis-                                              tatrienoic acid prostatrienoic acid                                           (Example 1378)                                                       1625     8β-methyl-9-oxo-11α,-                                                              8β-methyl-9α/β,11α,-                    15-dihydroxy-4a,4b-                                                                           15-trihydroxy-4a,4b-                                          bis-homo-5-cis,13-                                                                            bis-homo-5-cis,13-                                            cis,17-cis-pros-                                                                              cis-17-cis-prosta-                                            tatrienoic acid trienoic acid                                                 (Example 1378)                                                       1626     8α-methyl-9-oxo-11α,-                                                             8α-methyl-9α/β,11α,-                   15-dihydroxy-4a,4b-                                                                           15-trihydroxy-4a,4b-                                          bis-homo-8-iso-5-cis,                                                                         bis-homo-8-iso-5-                                             13-cis-17-cis-pros-                                                                           cis,13-cis,17-cis-                                            tatrienoic acid prostatrienoic acid                                           (Example 1378)                                                       1627     methyl 8β-methyl-9-                                                                      methyl 8β-methyl-                                        oxo-11α,15-dihydroxy-                                                                   9α/β,11α,15-tri-                             20-methyl-13-trans-                                                                           hydroxy-20-methyl-                                            prostenoate     13-trans-prostenoate                                          (Example 1379)                                                       1628     methyl 8α-methyl-9-                                                                     methyl 8α-methyl-                                       oxo-11α,15-dihydroxy-                                                                   9α/β,11α,15-tri-                             20-methyl-8-iso-13-                                                                           hydroxy-20-methyl-                                            trans-prostenoate                                                                             8-iso-13-trans-pros-                                          (Example 1379)  tenoate                                              1629     methyl 8β-methyl-9-                                                                      methyl 8β-methyl-                                        oxo-11α,15-dihydroxy-                                                                   9α/β,11α,15-tri-                             20-methyl-13-cis-                                                                             hydroxy-20-methyl-                                            prostenoate     13-cis-prostenoate                                            (Example 1379)                                                       1630     methyl 8β-methyl-9-                                                                      methyl 8α-methyl-                                       oxo-11α,15-dihydroxy-                                                                   9α/β,11α,15-tri-                             20-methyl-8-iso-13-                                                                           hydroxy-20-methyl-                                            cis-prostenoate 8-iso-13-cis-pros-                                            (Example 1379)  tenoate                                              1631     ethyl 8β -methyl-9-                                                                      ethyl 8β-methyl-                                         oxo-11α,15-dihydroxy-                                                                   9α/β,11α,15-tri-                             7a,7b-bis-homo-13-                                                                            hydroxy-7a,7b-bis-                                            trans,17-cis-prosta-                                                                          homo-13-trans,17-                                             dienoate        cis-prostadienoate                                            (Example 1380)                                                       1632     ethyl 8α-methyl-9-                                                                      ethyl 8α-methyl-9α/-                              oxo-11α,15-dihydroxy-                                                                   β,11α,15-trihydroxy-                               7a,7b-bis-homo-8-iso-                                                                         7a,7b-bis-homo-8-                                             13-trans,17-cis-                                                                              iso-13-trans,17-cis-                                          prostadienoate  prostadienoate                                                (Example 1380)                                                       1633     ethyl 8β-methyl-9-                                                                       ethyl 8β-methyl-                                         oxo-11α,15-dihydroxy-                                                                   9α/β,11α,15-tri-                             7a,7b-bis-homo-13-                                                                            hydroxy-7a,7b-bis-                                            cis-17-cis-prosta-                                                                            homo-13-cis,17-cis-                                           dienoate        prostadienoate                                                (Example 1380)                                                       1634     ethyl 8α-methyl-9-                                                                      ethyl 8α-methyl-                                        oxo-11α,15-dihydroxy-                                                                   9α/β,11α,15-tri-                             7a,7b-bis-homo-8-                                                                             hydroxy-7a,7b-bis-                                            iso-13-cis,17-cis-                                                                            homo-8-iso-13-cis-                                            prostadienoate  17-cis-prosta-                                                (Example 1380)  dienoate                                             1635     ethyl 8β-methyl-9-                                                                       ethyl 8β-methyl-                                         oxo-11α,15-dihydroxy-                                                                   9α/β,11α,15-tri-                             2-ethyl-16,16-dimeth-                                                                         hydroxy-2-ethyl-16,                                           yl-13-trans-prosten-                                                                          16-dimethyl-13-                                               oate            trans-prostenoate                                             (Example 1381)                                                       1636     ethyl 8α-methyl-9-                                                                      ethyl 8α-methyl-                                        oxo-11α,15-dihydroxy-                                                                   9α/β,11α,15-tri-                             2-ethyl-16,16-di-                                                                             hydroxy-2-ethyl-                                              methyl-8-iso-13-                                                                              16,16-dimethyl-8-                                             trans-prostenoate                                                                             iso-13-trans-pros-                                            (Example 1381)  tenoate                                              1637     ethyl 8β-methyl-9-                                                                       ethyl 8β-methyl-                                         oxo-11α,15-dihydroxy-                                                                   9α/β,11α,15-tri-                             2-ethyl-16,16-di-                                                                             hydroxy-2-ethyl-                                              methyl-13-cis-pros-                                                                           16,16-dimethyl-13-                                            tenoate         cis-prostenoate                                               (Example 1381)                                                       1638     ethyl 8α-methyl-9-                                                                      ethyl 8α-methyl-                                        oxo-11α,15-dihydroxy-                                                                   9α/β,11α,15-tri-                             2-ethyl-16,16-di-                                                                             hydroxy-2-ethyl-16,-                                          methyl-8-iso-13-cis-                                                                          16-dimethyl-8-iso-                                            prostenoate     13-cis-prostenoate                                            (Example 1381)                                                       1639     ethyl 8β-methyl-9-                                                                       ethyl 8β-methyl-                                         oxo-11α,15-dihydroxy-                                                                   9α/β,11α,15-tri-                             3,3,17,17-tetra-                                                                              hydroxy-3,3,17,17-                                            methyl-13-trans-                                                                              tetramethyl-13-                                               prostenoate     trans-prostenoate                                             (Example 1382)                                                       1640     ethyl 8α-methyl-9-                                                                      ethyl 8α-methyl-                                        oxo-11α,15-dihydroxy-                                                                   9α/β,11α,15-tri-                             3,3,17,17-tetra-                                                                              hydroxy-3,3,17,17-                                            methyl-8-iso-13-                                                                              tetramethyl-8-iso-                                            trans-prostenoate                                                                             13-trans-prosten-                                             (Example 1382)  oate                                                 1641     ethyl 8β-methyl-9-                                                                       ethyl 8β-methyl-                                         oxo-11α,15-dihydroxy-                                                                   9α/β,11α,15-tri-                             3,3,17,17-tetramethyl-                                                                        hydroxy-3,3,17,17-                                            13-cis-prostenoate                                                                            tetramethyl-13-cis-                                           (Example 1382)  prostenoate                                          1642     ethyl 8α-methyl-9-                                                                      ethyl 8α-methyl-                                        oxo-11α,15-dihydroxy-                                                                   9α/β,11α,15-tri-                             3,3,17,17-tetramethyl-                                                                        hydroxy-3,3,17,17-                                            8-iso-13-cis-prosten-                                                                         tetramethyl-8-iso-                                            oate            13-cis-prostenoate                                            (Example 1382)                                                       1643     ethyl 8β-methyl-9-                                                                       ethyl 8β-methyl-                                         oxo-11α,15-dihydroxy-                                                                   9α/β,11α,15-tri-                             3-oxa-17,17-dimethyl-                                                                         hydroxy-3-oxa-17,17-                                          13-trans-prostenoate                                                                          dimethyl-13-trans-                                            (Example 1383)  prostenoate                                          1644     ethyl 8α-methyl-9-                                                                      ethyl 8α-methyl-                                        oxo-11α,15-dihydroxy-                                                                   9α/β,11α,15-tri-                             3-oxa-17,17-dimethyl-                                                                         hydroxy-3-oxa-17,17-                                          8-iso-13-trans-pros-                                                                          dimethyl-8-iso-13-                                            tenoate         trans-prostenoate                                             (Example 1383)                                                       1645     ethyl 8β-methyl-9-                                                                       ethyl 8β-methyl-                                         oxo-11α,15-dihydroxy-                                                                   9α/β,11α,15-tri-                             3-oxa-17,17-dimethyl-                                                                         hydroxy-3-oxa-17,17-                                          13-cis-prostenoate                                                                            dimethyl-13-cis-                                              (Example 1383)  prostenoate                                          1646     ethyl 8α-methyl-9-                                                                      ethyl 8α-methyl-                                        oxo-11α,15-dihydroxy-                                                                   9α/β,11α,15-tri-                             3-oxa-17,17-dimethyl-                                                                         hydroxy-3-oxa-17,17-                                          8-iso-13-cis-pros-                                                                            dimethyl-8-iso-13-                                            tenoate         cis-prostenoate                                               (Example 1383)                                                       1647     butyl 8β-methyl-9-                                                                       butyl 8β-methyl-                                         oxo-11α,15-dihydroxy-                                                                   9α/β,11α,15-tri-                             13-trans-prostenoate                                                                          hydroxy-13-trans-                                             (Example 1384)  prostenoate                                          1648     butyl 8α-methyl-9-                                                                      butyl 8α-methyl-                                        oxo-11α,15-dihydroxy-                                                                   9α/β,11α,15-tri-                             8-iso-13-trans- hydroxy-8-iso-13-                                             prostenoate     trans-prostenoate                                             (Example 1384)                                                       1649     butyl 8β-methyl-9-                                                                       butyl 8β-methyl-                                         oxo-11α,15-dihydroxy-                                                                   9α/β,11α,15-tri-                             13-cis-prostenoate                                                                            hydroxy-13-cis-                                               (Example 1384)  prostenoate                                          1650     butyl 8α-methyl-9-                                                                      butyl 8α-methyl-                                        oxo-11α,15-dihydroxy-                                                                   9α/β,11α,15-tri-                             8-iso-13-cis-pros-                                                                            hydroxy-8-iso-13-                                             tenoate         cis-prostenoate                                               (Example 1384)                                                       1651     decyl 8β-methyl-9-                                                                       decyl 8β-methyl-                                         oxo-11α,15-dihydroxy-                                                                   9α/β,11α,15-tri-                             13-trans,17-cis-                                                                              hydroxy-13-trans,-                                            prostadienoate  17-cis-prosta-                                                (Example 1385)  dienoate                                             1652     decyl 8α-methyl-9-                                                                      decyl 8α-methyl-                                        oxo-11α,15-dihydroxy-                                                                   9α/β,11α,15-tri-                             8-iso-13-trans,17-                                                                            hydroxy-8-iso-13-                                             cis-prostadienoate                                                                            trans,17-cis-pro-                                             (Example 1385)  stadienoate                                          1653     decyl 8β-methyl-9-                                                                       decyl 8β-methyl-                                         oxo-11α,15-dihydroxy-                                                                   9α/β,11α,15-tri-                             13-cis,17-cis-pros-                                                                           hydroxy-13-cis,17-                                            tadienoate      cis-prostadienoate                                            (Example 1385)                                                       1654     decyl 8α-methyl-9-                                                                      decyl 8α-methyl-                                        oxo-11α,15-dihydroxy-                                                                   9α/β,11α,15-tri-                             8-iso-13-cis,17-cis-                                                                          hydroxy-8-iso-13-                                             prostadienoate  cis,17-cis-prosta-                                            (Example 1385)  dienoate                                             ______________________________________                                    

EXAMPLES 1655-1781

Saponification of the alkyl esters designated in Table 43 below by theprocedure described in Example 495 is productive of the carboxylic acidsof the table. The epimeric 9α and 9β hydroxy products are separable bythe usual chromatographic procedures.

                  TABLE 43                                                        ______________________________________                                        Ex-     Starting alkyl                                                        ample   prostenoate   Product prostenoic acid                                 ______________________________________                                        1655    11-deoxy-8β-meth-                                                                      11-deoxy-8β-methyl-pros-                                   yl-prostaglandin                                                                            taglandin E.sub.1                                               E.sub.1 methyl ester                                                          (Example 1188)                                                        1656    11-deoxy-8α-meth-                                                                     11-deoxy-8α-methyl-8-                                     yl-8-iso-prosta-                                                                            iso-prostaglandin E.sub.1                                       glandin E.sub.1 meth-                                                         yl ester (Exam-                                                               ple 1188)                                                             1657    methyl 15-hy- 15-hydroxy-8β-methyl-8-                                    droxy-8β-methyl                                                                        oxo-13-cis-prostenoic                                           9-oxo-13-cis- acid                                                            prostenoate                                                                   (Example 1188)                                                        1658    methyl-15-hy- 15 hydroxy-8α-methyl-8-                                   droxy-8α-methyl-                                                                      iso-9-oxo-13-cis-                                               8-iso-9-oxo-13-                                                                             prostenoic acid                                                 cis-prostenoate                                                               (Example 1188)                                                        1659    11-deoxy-8β-meth-                                                                      11-deoxy-8β-methyl-                                        yl-prostaglandin                                                                            prostaglandin F.sub.1 α/β                            F.sub.1 α/β methyl                                                 esters (Ex. 1206)                                                     1660    11-deoxy-8α-meth-                                                                     11-deoxy-8α-methyl-8-                                     yl-8-iso-prosta-                                                                            iso-prostaglandin                                               glandin F.sub.1 α/β                                                              F.sub.1 α/β                                          methyl esters                                                                 (Example 1207)                                                        1661    methyl 9α,15-di-                                                                      9α,15-dihydroxy-8β-meth-                             hydroxy-8β-meth-                                                                       yl-13-cis-prostenoic                                            yl-13-cis-pros-                                                                             acid                                                            tenoate (Example                                                              1208)                                                                 1662    ethyl 8β-methyl-                                                                       8β-methyl-9-oxo-15-hy-                                     9-oxo-15-hy-  droxy-16,16-dimethyl-13-                                        droxy-16,16-di-                                                                             trans-prostenoic acid                                           methyl-13-trans-                                                              prostenoate                                                                   (Example 1190)                                                        1663    ethyl 8α-methyl-                                                                      8α-methyl-9-oxo-15-hy-                                    9-oxo-15-hy-  droxy-16,16-dimethyl-8-                                         droxy-16,16-di-                                                                             iso-13-trans-prosten-                                           methyl-8-iso-13-                                                                            oic acid                                                        trans-prosteno-                                                               ate (Example                                                                  1190)                                                                 1664    ethyl 8β-methyl-                                                                       8β-methyl-9-oxo-15-hy-                                     9-oxo-15-hy-  droxy-16,16-dimethyl-                                           droxy-16,16-di-                                                                             13-cis-prostenoic acid                                          methyl-13-cis-                                                                prostenoate                                                                   (Example 1190)                                                        1665    ethyl 8α-methyl-                                                                      8α-methyl-9-oxo-15-hy-                                    9-oxo-15-hy-  droxy-16,16-dimethyl-                                           droxy-16,16-di-                                                                             8-iso-13-cis-prosten-                                           methyl-8-iso-13-                                                                            oic acid                                                        cis-prostenoate                                                               (Example 1190)                                                        1666    ethyl 8β-methyl-                                                                       8β-methyl-9-oxo-15-hy-                                     9-oxo-15-hy-  droxy-17,17-dimethyl-                                           droxy-17,17-di-                                                                             13-trans-prostenoic                                             methyl-13-trans-                                                                            acid                                                            prostenoate                                                                   (Example 1191)                                                        1667    ethyl 8α-methyl-                                                                      8α-methyl-9-oxo-15-hy-                                    9-oxo-15-hy-  droxy-17,17-dimethyl-                                           droxy-17,17-di-                                                                             8-iso-13-trans-pros-                                            methyl-8-iso-13-                                                                            tenoic acid                                                     trans-prosteno-                                                               ate (Example                                                                  1191                                                                  1668    ethyl 8β-methyl-                                                                       8β-methyl-9-oxo-15-hy-                                     9-oxo-15-hy-  droxy-17,17-dimethyl-                                           droxy-17,17-di-                                                                             13-cis-prostenoic acid                                          methyl-13-cis-                                                                prostenoate                                                                   (Example 1191)                                                        1669    ethyl 8α-methyl-                                                                      8α-methyl-9-oxo-15-hy-                                    9-oxo-15-hy-  droxy-17,17-dimethyl-8-                                         droxy-17,17-di-                                                                             iso-13-cis-prostenoic                                           methyl-8-iso-13-                                                                            acid                                                            cis-prostenoate                                                               (Example 1191)                                                        1670    ethyl 8β-methyl-                                                                       8β-methyl-9-oxo-15-hy-                                     9-oxo-15-hy-  droxy-13-trans,17-cis-                                          droxy-13-trans,-                                                                            prostadienoic acid                                              17-cis-prostadi-                                                              enoate (Example                                                               1192)                                                                 1671    ethyl 8α-methyl-                                                                      8α-methyl-9-oxo-15-hy-                                    9-oxo-15-hy-  droxy-8-iso-13-trans,17-                                        droxy-8-iso-13-                                                                             cis-prostadienoic acid                                          trans,17-cis-                                                                 prostadienoate                                                                (Example 1192)                                                        1672    ethyl 8β-methyl-                                                                       8β-methyl-9-oxo-15-hy-                                     9-oxo-15-hy-  droxy-13-cis,17-cis-                                            droxy-13-cis,17-                                                                            prostadienoic acid                                              cis-prostadien-                                                               oate (Example                                                                 1192)                                                                 1673    ethyl 8α-methyl-                                                                      8α-methyl-9-oxo-15-hy-                                    9-oxo-15-hy-  droxy-8-iso-13-cis,17-                                          droxy-8-iso-13-                                                                             cis-prostadienoic acid                                          cis,17-cis-pros-                                                              tadienoate (Ex-                                                               ample 1192)                                                           1674    ethyl 8β-methyl-                                                                       8β-methyl-9-oxo-15-hy-                                     9-oxo-15-hy-  droxy-20-ethyl-13-trans-                                        droxy-20-ethyl-                                                                             prostenoic acid                                                 13-trans-pros-                                                                tenoate (Example                                                              1193)                                                                 1675    ethyl 8α-methyl-                                                                      8α-methyl-9-oxo-15-hy-                                    9-oxo-15-hy-  droxy-20-ethyl-8-iso-13-                                        droxy-20-ethyl-                                                                             trans-prostenoic acid                                           8-iso-13-trans-                                                               prostenoate                                                                   (Example 1193)                                                        1676    ethyl 8β-methyl-                                                                       8β-methyl-9-oxo-15-hy-                                     9-oxo-15-hy-  droxy-20-ethyl-13-cis-                                          droxy-20-ethyl-                                                                             prostenoic acid                                                 13-cis-prosten-                                                               oate (Example                                                                 1193)                                                                 1677    ethyl 8α-methyl-                                                                      8α-methyl-9-oxo-15-hy-                                    9-oxo-15-hy-  droxy-20-ethyl-8-iso-13-                                        droxy-20-ethyl-                                                                             cis-prostenoic acid                                             8-iso-13-cis-                                                                 prostenoate                                                                   (Example 1193)                                                        1678    ethyl 8β-methyl-                                                                       8β-methyl-9-oxo-15-hy-                                     9-oxo-15-hy-  droxy-7a,7b-bishomo-13-                                         droxy-7a,7b-bis-                                                                            trans-prostenoic acid                                           homo-13-trans-                                                                prostenoate                                                                   (Example 1195)                                                        1679    ethyl 8α-methyl-                                                                      8α-methyl-9-oxo-15-hy-                                    9-oxo-15-hy-  droxy-7a,7b-bishomo-8-                                          droxy-7a,7b-bis-                                                                            iso-13-trans-prostenoic                                         homo-8-iso-13-                                                                              acid                                                            trans-prosteno-                                                               ate (Example                                                                  1195)                                                                 1680    ethyl 8β-methyl-                                                                       8β-methyl-9-oxo-15-hy-                                     9-oxo-15-hy-  droxy-7a,7b-bishomo-13-                                         droxy-7a,7b-bis-                                                                            cis-prostenoic acid                                             homo-13-cis-                                                                  prostenoate                                                                   (Example 1195)                                                        1681    ethyl 8α-methyl-                                                                      8α-methyl-9-oxo-15-hy-                                    9-oxo-15-hy-  droxy-7a,7b-bishomo-8-                                          droxy-7a,7b-bis-                                                                            iso-13-cis-prostenoic                                           homo-8-iso-13-                                                                              acid                                                            cis-prostenoate                                                               (Example 1195)                                                        1682    ethyl 8β-methyl-                                                                       8β-methyl-9-oxo-15-hy-                                     9-oxo-15-hy-  droxy-2,20-bisethyl-13-                                         droxy-2,20-bis-                                                                             trans-prostenoic acid                                           ethyl-13-trans-                                                               prostenoate                                                                   (Example 1196)                                                        1683    ethyl 8α-methyl-                                                                      8α -methyl-9-oxo-15-hy-                                   9-oxo-15-hy-  droxy-2,20-bisethyl-8-                                          droxy-2,20-bis-                                                                             iso-13-trans-prostenoic                                         ethyl-8-iso-13-                                                                             acid                                                            trans-prosten-                                                                oate (Example                                                                 1196)                                                                 1684    ethyl 8β-methyl-                                                                       8β-methyl-9-oxo-15-hy-                                     9-oxo-15-hy-  droxy-2,20-bisethyl-13-                                         droxy-2,20-bis-                                                                             cis-prostenoic acid                                             ethyl-13-cis-                                                                 prostenoate                                                                   (Example 1196)                                                        1685    ethyl 8α-methyl-                                                                      8α-methyl-9-oxo-15-hy-                                    9-oxo-15-hy-  droxy-2,20-bisethyl-8-                                          droxy-2,20-bis-                                                                             iso-13-cis-prostenoic                                           ethyl-8-iso-13-                                                                             acid                                                            cis-prostenoate                                                               (Example 1196)                                                        1686    ethyl 8β-methyl-                                                                       8β-methyl-9-oxo-15-hy-                                     9-oxo-15-hy-  droxy-3-oxa-16,16-di-                                           droxy-3-oxa-16,-                                                                            methyl-13-trans-pros-                                           16-dimethyl-13-                                                                             tenoic acid                                                     trans-prosteno-                                                               ate (Example                                                                  1197)                                                                 1687    ethyl 8α-methyl-                                                                      8α-methyl-9-oxo-15-hy-                                    9-oxo-15-hy-  droxy-3-oxa-16,16-di-                                           droxy-3-oxa-16,-                                                                            methyl-8-iso-13-trans-                                          16-dimethyl 8-                                                                              prostenoic acid                                                 iso-13-trans-                                                                 prostenoate                                                                   (Example 1197)                                                        1688    ethyl 8β-methyl-                                                                       8β-methyl-9-oxo-15-hy-                                     9-oxo-15-hy-  droxy-3-oxa-16,16-di-                                           droxy-3-oxa-16,-                                                                            methyl-13-cis-prostenoic                                        16-dimethyl-13-                                                                             acid                                                            cis-prostenoate                                                               (Example 1197)                                                        1689    ethyl 8α-methyl-                                                                      8α-methyl-9-oxo-15-hy-                                    9-oxo-15-hy-  droxy-3-oxa-16,16-di-                                           droxy-3-oxa-16,-                                                                            methyl-8-iso-13-cis-                                            16-dimethyl-8-iso-                                                                          prostenoic acid                                                 13-cis-prosteno-                                                              ate (Example 1197)                                                    1690    ethyl 8β-methyl-                                                                       8β-methyl-9-oxo-15-hy-                                     9-oxo-15-hy-  droxy-3-oxa-13-trans,-                                          droxy-3-oxa-13-                                                                             17-cis-prostadienoic                                            trans,17-cis- acid                                                            prostadienoate                                                                (Example 1198)                                                        1691    ethyl 8α-methyl-                                                                      8α-methyl-9-oxo-15-hy-                                    9-oxo-15-hy-  droxy-3-oxa-8-iso-13-                                           droxy-3-oxa-8-                                                                              trans,17-cis-prostadi-                                          iso-13-trans,17-                                                                            enoic acid                                                      cis-prostadieno-                                                              ate (Example                                                                  1198)                                                                 1692    ethyl 8β-methyl-                                                                       8β-methyl-9-oxo-15-hy-                                     9-oxo-15-hy-  droxy-3-oxa-13-cis,17-                                          droxy-3-oxa-13-                                                                             cis-prostadienoic acid                                          cis,17-cis-pros-                                                              tadienoate (Exam-                                                             ple 1198)                                                             1693    ethyl 8α-methyl-                                                                      8α-methyl-9-oxo-15-hy-                                    9-oxo-15-hy-  droxy-3-oxa-8-iso-13-                                           droxy-3-oxa-8-                                                                              cis,17-cis-prostadi-                                            iso-13-cis,17-                                                                              enoic acid                                                      cis-prostadieno-                                                              ate (Example                                                                  1198)                                                                 1694    ethyl 8β-methyl-                                                                       8β-methyl-9-oxo-15-hy-                                     9-oxo-15-hy-  droxy-7-nor-20-methyl-                                          droxy-7-nor-20-                                                                             13-trans-prostenoic                                             methyl-13-trans-                                                                            acid                                                            prostenoate                                                                   (Example 1199)                                                        1695    ethyl 8α-methyl-                                                                      8α-methyl-9-oxo-15-hy-                                    9-oxo-15-hy-  droxy-7-nor-20-methyl-                                          droxy-7-nor-20-                                                                             8-iso-13-trans-pros-                                            methyl-8-iso- tenoic acid                                                     13-trans-pros-                                                                tenoate (Example                                                              1199)                                                                 1696    ethyl 8β-methyl-                                                                       8β-methyl-9-oxo-15-hy-                                     9-oxo-15-hy-  droxy-7-nor-20-methyl-                                          droxy-7-nor-20-                                                                             13-cis-prostenoic acid                                          methyl-13-cis-                                                                prostenoate                                                                   (Example 1199)                                                        1697    ethyl 8α-methyl-                                                                      8α-methyl-9-oxo-15-hy-                                    9-oxo-15-hy-  droxy-7-nor-20-methyl-                                          droxy-7-nor-20-                                                                             8-iso-13-cis-prosteno-                                          methyl-8-iso- ic acid                                                         13-cis-prosten-                                                               oate (Example                                                                 1199)                                                                 1698    ethyl 8β-methyl-                                                                       8β-methyl-9-oxo-15-hy-                                     9-oxo-15-hy-  droxy-2-fluoro-17,17-di-                                        droxy-2-fluoro-                                                                             methyl-13-trans-pros-                                           17,17-dimethyl-                                                                             tenoic acid                                                     13-trans-pros-                                                                tenoate (Example                                                              1200)                                                                 1699    ethyl 8α-methyl-                                                                      8α-methyl-9-oxo-15-hy-                                    9-oxo-15-hy-  droxy-2-fluoro-17,17-                                           droxy-2-fluoro-                                                                             dimethyl-8-iso-13-                                              17,17-dimethyl-                                                                             trans-prostenoic acid                                           8-iso-13-trans-                                                               prostenoate                                                                   (Example 1200)                                                        1700    ethyl 8β-methyl-                                                                       8β-methyl-9-oxo-15-hy-                                     9-oxo-15-hy-  droxy-2-fluoro-17,17-                                           droxy-2-fluoro-                                                                             dimethyl-13-cis-                                                17,17-dimethyl-                                                                             prostenoic acid                                                 13-cis-prosten-                                                               oate (Example                                                                 1200)                                                                 1701    ethyl 8α-methyl-                                                                      8α-methyl-9-oxo-15-hy-                                    9-oxo-15-hy-  droxy-2-fluoro-17,17-                                           droxy-2-fluoro-                                                                             dimethyl-8-iso-13-cis-                                          17,17-dimethyl-                                                                             prostenoic acid                                                 8-iso-13-cis-                                                                 prostenoate                                                                   (Example 1200)                                                        1702    ethyl 8β-methyl-                                                                       8β-methyl-9-oxo-15-hy-                                     9-oxo-15-hy-  droxy 10a-homo-13-                                              droxy-10a-homo-                                                                             trans-prostenoic acid                                           13-trans-pros-                                                                tenoate (Example                                                              1201)                                                                 1703    ethyl 8α-methyl-                                                                      8α-methyl-9-oxo-15-hy-                                    9-oxo-15-hy-  droxy-10a-homo-8-iso-                                           droxy-10a-homo-8-                                                                           13-trans-prostenoic                                             iso-13-trans- acid                                                            prostenoate                                                                   (Example 1201)                                                        1704    ethyl 8β-methyl-                                                                       8β-methyl-9-oxo-15-hy-                                     9-oxo-15-hy-  droxy-10a-homo-13-cis-                                          droxy-10a-homo-                                                                             prostenoic acid                                                 13-cis-prosten-                                                               oate (Example                                                                 1201)                                                                 1705    ethyl 8α-methyl-                                                                      8α-methyl-9-oxo-15-hy-                                    9-oxo-15-hy-  droxy-10a-homo-8-iso-                                           droxy-10a-homo-                                                                             13-cis-prostenoic acid                                          8-iso-13-cis-                                                                 prostenoate                                                                   (Example 1201)                                                        1706    ethyl 8β-methyl-                                                                       8β-methyl-9-oxo-15-hy-                                     9-oxo-15-hy-  droxy-2-phenyl-20-meth-                                         droxy-2-phenyl-                                                                             yl-13-trans-prostenoic                                          20-methyl-13- acid                                                            trans-prosteno-                                                               ate (Example                                                                  1202)                                                                 1707    ethyl 8α-methyl-                                                                      8α-methyl-9-oxo-15-hy-                                    9-oxo-15-hy-  droxy-2-phenyl-20-meth-                                         droxy-2-phenyl-                                                                             yl-8-iso-13-trans-pros-                                         20-methyl-8-iso-                                                                            tenoic acid                                                     13-trans-pros-                                                                tenoate (Example                                                              1202)                                                                 1708    ethyl 8β-methyl-                                                                       8β-methyl-9-oxo-15-hy-                                     9-oxo-15-hy-  droxy-2-phenyl-20-meth-                                         droxy-2-phenyl-                                                                             yl-13-cis-prostenoic                                            20-methyl-13- acid                                                            cis-prostenoate                                                               (Example 1202)                                                        1709    ethyl 8α-methyl-                                                                      8α-methyl-9-oxo-15-hy-                                    9-oxo-15-hy-  droxy-2-phenyl-20-meth-                                         droxy-2-phenyl-                                                                             yl-8-iso-13-cis-prosten-                                        20-methyl-8-iso-                                                                            oic acid                                                        13-cis-prosten-                                                               oate (Example                                                                 1202)                                                                 1710    methyl 8β-methyl-                                                                      8β-methyl-9-oxo-15-hy-                                     9-oxo-15-hy-  droxy-5-cis,13-trans,17-                                        droxy-5-cis,13-                                                                             cis-prostatrienoic acid                                         trans,17-cis-                                                                 prostatrienoate                                                               (Example 1203)                                                        1711    methyl 8α-methyl-                                                                     8α-methyl-9-oxo-15-hy-                                    9-oxo-15-hy-  droxy-8-iso-5-cis,13-                                           droxy-8-iso-5-                                                                              trans,17-cis-prostatri-                                         cis,13-trans,17-                                                                            enoic acid                                                      cis-prostatrien-                                                              oate (Example                                                                 1203)                                                                 1712    methyl 8β-methyl-                                                                      8β-methyl-9-oxo-15-hy-                                     9-oxo-15-hy-  droxy-5-cis,13-cis,17-                                          droxy-5-cis,13-                                                                             cis-prostatrienoic acid                                         cis,17-cis-pros-                                                              tatrienoate                                                                   (Example 1203)                                                        1713    methyl 8α-methyl-                                                                     8α-methyl-9-oxo-15-hy-                                    9-oxo-15-hy-  droxy-8-iso-5-cis,13-                                           droxy-8-iso-5-                                                                              cis,17-cis-prostatri-                                           cis,13-cis,17-                                                                              enoic acid                                                      cis-prostatrien-                                                              oate (Example                                                                 1203)                                                                 1714    ethyl 8β-methyl-                                                                       8β-methyl-9-oxo-15-hy-                                     9-oxo-15-hy-  droxy-5-cis,13-trans-                                           droxy-5-cis,13-                                                                             prostadienoic acid                                              trans-prostadi-                                                               enoate (Example                                                               1204)                                                                 1715    ethyl 8α-methyl-                                                                      8α-methyl-9-oxo-15-hy-                                    9-oxo-15-hy-  droxy-8-iso-5-cis,13-                                           droxy-8-iso-5-                                                                              trans-prostadienoic                                             cis,13-trans- acid                                                            prostadienoate                                                                (Example 1204)                                                        1716    ethyl 8β-methyl-                                                                       8β-methyl-9-oxo-15-hy-                                     9-oxo-15-hy-  droxy-5-cis,13-cis-                                             droxy-5-cis,13-                                                                             prostadienoic acid                                              cis-prostadieno-                                                              ate (Example                                                                  1204)                                                                 1717    ethyl 8α-methyl-                                                                      8α-methyl-9-oxo-15-hy-                                    9-oxo-15-hy-  droxy-8-iso-5-cis,13-                                           droxy-8-iso-5-                                                                              cis-prostadienoic acid                                          cis,13-cis-pros-                                                              tadienoate (Exam-                                                             ple 1204)                                                             1718    ethyl 8β-methyl-                                                                       8β-methyl-9-oxo-15-hy-                                     9-oxo-15-hy-  droxy-20-ethyl-5-cis,13-                                        droxy-20-ethyl-                                                                             trans-prostadienoic acid                                        5-cis,13-trans-                                                               prostadienoate                                                                (Example 1205)                                                        1719    ethyl 8α-methyl-                                                                      8α-methyl-9-oxo-15-hy-                                    9-oxo-15-hy-  droxy-20-ethyl-8-iso-5-                                         droxy-20-ethyl-                                                                             cis,13-trans-prostadi-                                          8-iso-5-cis,13-                                                                             enoic acid                                                      trans-prostadi-                                                               enoate (Example                                                               1205)                                                                 1720    ethyl 8β-methyl-                                                                       8β-methyl-9-oxo-15-hy-                                     9-oxo-15-hy-  droxy-20-ethyl-5-cis,13-                                        droxy-20-ethyl-                                                                             cis-prostadienoic acid                                          5-cis,13-cis-                                                                 prostadienoate                                                                (Example 1205)                                                        1721    ethyl 8α-methyl-                                                                      8α-methyl-9-oxo-15-hy-                                    9-oxo-15-hy-  droxy-20-ethyl-8-iso-                                           droxy-20-ethyl-                                                                             5-cis,13-cis-prosta-                                            8-iso-5-cis,13-                                                                             dienoic acid                                                    cis-prostadien-                                                               oate (Example                                                                 1205)                                                                 ______________________________________                                                Starting alkyl                                                        Ex-     ester of                                                              ample   Example       Product prostenoic acid                                 ______________________________________                                        1722    1210          8β-methyl-9α/β,15-dihy-                                       droxy-16,16-dimethyl-13-                                                      trans-prostenoic acid                                   1723    1211          8α-methyl-9α/β,15-di-                                        hydroxy-16,16-dimethyl-                                                       8-iso-13-trans-pros-                                                          tenoic acid                                             1724    1212          8β-methyl-9α/β,15-dihy-                                       droxy-16,16-dimethyl-13-                                                      cis-prostenoic acid                                     1725    1213          8α-methyl-9α/β,15-dihy-                                      droxy-16,16-dimethyl-                                                         8-iso-13-cis-prostenoic                                                       acid                                                    1726    1214          8β-methyl-9α/β,15-dihy-                                       droxy-17,17-dimethyl-                                                         13-trans-prostenoic                                                           acid                                                    1727    1215          8α-methyl-9α/β,15-dihy-                                      droxy-17,17-dimethyl-8-                                                       iso-13-trans-prosten-                                                         oic acid                                                1728    1216          8β-methyl-9α/β,15-dihy-                                       droxy-17,17-dimethyl-13-                                                      cis-prostenoic acid                                     1729    1217          8α-methyl-9α/β,15-dihy-                                      droxy-17,17-dimethyl-8-                                                       iso-13-cis-prostenoic                                                         acid                                                    1730    1218          8β-methyl-9α/β,15-dihy-                                       droxy-13-trans,17-cis-                                                        prostadienoic acid                                      1731    1219          8α-methyl-9α/β,15-dihy-                                      droxy-8-iso-13-trans,17-                                                      cis-prostadienoic acid                                  1732    1220          8β-methyl-9α/β,15-dihy-                                       droxy-13-cis,17-cis-                                                          prostadienoic acid                                      1733    1221          8α-methyl-9α /β,15-dihy-                                     droxy-8-iso-13-cis,17-                                                        cis-prostadienoic acid                                  1734    1222          8β-methyl-9α/β,15-dihy-                                       droxy-20-ethyl-13-trans-                                                      prostenoic acid                                         1735    1223          8α-methyl-9α/β,15-dihy-                                      droxy-20-ethyl-8-iso-                                                         13-trans-prostenoic                                                           acid                                                    1736    1224          8β-methyl-9α/β,15-dihy-                                       droxy-20-ethyl-13-cis-                                                        prostenoic acid                                         1737    1225          8α-methyl-9α/β,15-dihy-                                      droxy-20-ethyl-8-iso-                                                         13-cis-prostenoic acid                                  1738    1230          8β-methyl-9α/β,15-dihy-                                       droxy-7a,7b-bishomo-13-                                                       trans-prostenoic acid                                   1739    1231          8α-methyl-9α/β,15-dihy-                                      droxy-7a,7b-bishomo-8-                                                        iso-13-trans-prosten-                                                         oic acid                                                1740    1232          8β-methyl-9α/β,15-dihy-                                       droxy-7a,7b-bishomo-13-                                                       cis-prostenoic acid                                     1741    1233          8α-methyl-9α/β,15-dihy-                                      droxy-7a,7b-bishomo-8-                                                        iso-13-cis-prostenoic                                                         acid                                                    1742    1234          8β-methyl-9α/β,15-dihy-                                       droxy-2,20-bisethyl-13-                                                       trans-prostenoic acid                                   1743    1235          8α-methyl-9α/β,15-dihy-                                      droxy-2,20-bisethyl-8-                                                        iso-13-trans-prosten-                                                         oic acid                                                1744    1236          8β-methyl-9α/β,15-dihy-                                       droxy-2,20-bisethyl-13-                                                       cis-prostenoic acid                                     1745    1237          8α-methyl-9α/β,15-dihy-                                      droxy-2,20-bisethyl-8-                                                        iso-13-cis-prostenoic                                                         acid                                                    1746    1238          8β-methyl-9α/β,15-dihy-                                       droxy-3-oxa-16,16-di-                                                         methyl-13-trans-pros-                                                         tenoic acid                                             1747    1239          8α-methyl-9α/β,15-dihy-                                      droxy-3-oxa-16,16-di-                                                         methyl-8-iso-13-trans-                                                        prostenoic acid                                         1748    1240          8β-methyl-9α/β,15-dihy-                                       droxy-3-oxa-16,16-di-                                                         methyl-13-cis-prosten-                                                        oic acid                                                1749    1241          8α-methyl-9α/β,15-dihy-                                      droxy-3-oxa-16,16-di-                                                         methyl-8-iso-13-cis-                                                          prostenoic acid                                         1750    1242          8β-methyl-9α/β,15-dihy-                                       droxy-3-oxa-13-trans,17-                                                      cis-prostadienoic acid                                  1751    1243          8α-methyl-9α/β,15-dihy-                                      droxy-3-oxa-8-iso-13-                                                         trans,17-cis-prostadi-                                                        enoic acid                                              1752    1244          8β-methyl-9α/β,15-dihy-                                       droxy-3-oxa-13-cis,17-                                                        cis-prostadienoic acid                                  1753    1245          8α-methyl-9α/β,15-dihy-                                      droxy-3-oxa-8-iso-13-                                                         cis,17-cis-prostadien-                                                        oic acid                                                1754    1246          8β-methyl-9α/β,15-dihy-                                       droxy-7-nor-20-methyl-                                                        13-trans-prostenoic                                                           acid                                                    1755    1247          8α-methyl-9α/β,15-dihy-                                      droxy-7-nor-20-methyl-                                                        8-iso-13-trans-pros-                                                          tenoic acid                                             1756    1248          8β-methyl-9α/β,15-dihy-                                       droxy-7-nor-20-methyl-                                                        13-cis-prostenoic acid                                  1757    1249          8α-methyl-9α/β,15-dihy-                                      droxy-7-nor-20-methyl-                                                        8-iso-13-cis-prosteno-                                                        ic acid                                                 1758    1250          8β-methyl-9α/β,15-dihy-                                       droxy-2-fluoro-17,17-                                                         dimethyl-13-trans-                                                            prostenoic acid                                         1759    1251          8α-methyl-9α/β,15-dihy-                                      droxy-2-fluoro-17,17-                                                         dimethyl-8-iso-13-                                                            trans-prostenoic acid                                   1760    1252          8β-methyl-9α/β,15-dihy-                                       droxy-2-fluoro-17,17-                                                         dimethyl-13-cis-pros-                                                         tenoic acid                                             1761    1253          8α-methyl-9α/β,15-dihy-                                      droxy-2-fluoro-17,17-                                                         dimethyl-8-iso-13-cis-                                                        prostenoic acid                                         1762    1254          8β-methyl-9α/β,15-dihy-                                       droxy-10a-homo-13-trans-                                                      prostenoic acid                                         1763    1255          8α-methyl-9α/β,15-dihy-                                      droxy-10a-homo-8-iso-                                                         13-trans-prostenoic                                                           acid                                                    1764    1256          8β-methyl-9α/β,15-dihy-                                       droxy-10a-homo-13-cis-                                                        prostenoic acid                                         1765    1257          8α-methyl-9α/β,15-dihy-                                      droxy-10a-homo-8-iso-                                                         13-cis-prostenoic acid                                  1766    1258          8β-methyl-9α/β,15-dihy-                                       droxy-2-phenyl-20-meth-                                                       yl-13-trans-prostenoic                                                        acid                                                    1767    1259          8α-methyl-9α/β,15-dihy-                                      droxy-2-phenyl-20-meth-                                                       yl-8-iso-13-trans-pros-                                                       tenoic acid                                             1768    1260          8β-methyl-9α/β,15-dihy-                                       droxy-2-phenyl-20-meth-                                                       yl-13-cis-prostenoic                                                          acid                                                    1769    1261          8α-methyl-9α/β,15-dihy-                                      droxy-2-phenyl-20-meth-                                                       yl-8-iso-13-cis-prosten-                                                      oic acid                                                1770    1262          8β-methyl-9α/β,15-dihy-                                       droxy-5-cis,13-trans,17-                                                      cis-prostatrienoic acid                                 1771    1263          8α-methyl-9α/β,15-dihy-                                      droxy-8-iso-5-cis,13-                                                         trans,17-cis-prostatri-                                                       enoic acid                                              1772    1264          8β-methyl-9α/β,15-dihy-                                       droxy-5-cis,13-cis,17-                                                        cis-prostatrienoic acid                                 1773    1265          8α-methyl-9α/β,15-dihy-                                      droxy-8-iso-5-cis,13-                                                         cis,17-cis-prostatri-                                                         enoic acid                                              1774    1266          8β -methyl-9α/β,15-dihy-                                      droxy-5-cis,13-trans-                                                         prostadienoic acid                                      1775    1267          8α-methyl-9α/β,15-dihy-                                      droxy-8-iso-5-cis,13-                                                         trans-prostadienoic                                                           acid                                                    1776    1268          8β-methyl-9α/β,15-dihy-                                       droxy-5-cis,13-cis-                                                           prostadienoic acid                                      1777    1269          8α-methyl-9α/β,15-dihy-                                      droxy-8-iso-5-cis,13-                                                         cis-prostadienoic acid                                  1778    1270          8β-methyl-9α/β,15-dihy-                                       droxy-20-ethyl-5-cis,13-                                                      trans-prostadienoic                                                           acid                                                    1779    1271          8α-methyl-9α/β,15-dihy-                                      droxy-20-ethyl-8-iso-                                                         5-cis,13-trans-pros-                                                          tadienoic acid                                          1780    1272          8β-methyl-9α/β,15-dihy-                                       droxy-20-ethyl-5-cis,-                                                        13-cis-prostadienoic                                                          acid                                                    1781    1273          8α-methyl-9α/β,15-dihy-                                      droxy-20-ethyl-8-iso-                                                         5-cis,13-cis-prosta-                                                          dienoic acid                                            ______________________________________                                    

EXAMPLES 1782-1815

Catalytic hydrogenation of the 13-trans-prostenoic acids or esterslisted below in Table 44 by the procedure described in Example 699furnishes the product prostanoic acids of the table.

                  TABLE 44                                                        ______________________________________                                                Starting 13-                                                                  trans-prostenoic                                                                             Products                                               Ex-     acid or ester of                                                                             8-methylprostanoic                                     ample   Example        acids or esters                                        ______________________________________                                        1782    1206           Methyl 8β-methyl-9α/β,                                        15-dihydroxy-                                                                 prostanoate                                            1783    1207           Methyl 8α-methyl-9α/β,                                       15-dihydroxy-8-iso-                                                           prostanoate                                            1784    1210           Ethyl 8β-methyl-9α/β,                                         15-dihydroxy-15,16-                                                           dimethyl-prostanoate                                   1785    1226           Decyl 8β-methyl-9α/β,                                         15-dihydroxy-20-methyl-                                                       prostanoate                                            1786    1655           8β-methyl-9-oxo-15-di-                                                   hydroxy-prostanoic acid                                1787    1656           8α-methyl-9-oxo-15-di-                                                  hydroxy-8-iso-prostan-                                                        oic acid                                               1788    1659           8β-methyl-9α/β,15-di-                                         hydroxy-prostanoic acid                                1789    1660           8α-methyl-9α/β,15-di-                                        hydroxy-8-iso-prostan-                                                        oic acid                                               1790    1678           8β-methyl-9-oxo-15-hy-                                                   droxy-7a,7b-bishomo-                                                          prostanoic acid                                        1791    1683           8α-methyl-9-oxo-15-                                                     hydroxy-2,20-bisethyl-                                                        8-iso-prostanoic acid                                  1792    1686           8β-methyl-9-oxo-15-                                                      hydroxy-3-oxa-16,16-                                                          dimethyl-prostanoic                                                           acid                                                   1793    1694           8β-methyl-9-oxo-15-                                                      hydroxy-7-nor-20-                                                             methyl-prostanoic acid                                 1794    1702           8β-methyl-9-oxo-15-                                                      hydroxy-10a-homo-                                                             prostanoic acid                                        1795    1523           8β-methyl-9α/β,11α,15-                                  trihydroxy-prostanoic                                                         acid                                                   1796    1524           8α-methyl-9α/β,11α,15-                                 trihydroxy-8-iso-                                                             prostanoic acid                                        1797    1527           8β-methyl-9α/β,11α,15-                                  trihydroxy-16,16-di-                                                          methyl-prostanoic acid                                 1798    1531           8β-methyl-9α/β,11α,15-                                  trihydroxy-17,17-di-                                                          methyl-prostanoic acid                                 1799    1539           8β-methyl-9α/β,11α,15-                                  trihydroxy-20-ethyl-                                                          prostanoic acid                                        1800    1552           8α-methyl-9α/β,11α,15-                                 trihydroxy-7a,7b-bis-                                                         homo-8-iso-prostanoic                                                         acid                                                   1801    1551           8β-methyl-9α/β,11α,15-                                  trihydroxy-7a,7b-bis-                                                         homo-prostanoic acid                                   1802    1555           8β-methyl-9α/β,11α,15-                                  trihydroxy-2-ethyl-                                                           prostanoic acid                                        1803    1559           8β-methyl-9α/β,11α,15-                                  trihydroxy-3,3,20-tri-                                                        methyl-prostanoic acid                                 1804    1563           8β-methyl-9α/β,11α,15-                                  trihydroxy-3-oxa-                                                             prostanoic acid                                        1805    1567           8β-methyl-9α/β,11α,15-                                  trihydroxy-3-oxa-16,                                                          16-dimethyl-prostanoic                                                        acid                                                   1806    1587           8β-methyl-9α/β,11α,15-                                  trihydroxy-7a-homo-                                                           16,16-dimethyl-pro-                                                           stanoic acid                                           1807    1643           Ethyl 8β-methyl-9α/β,                                         11α,15-trihydroxy-3-                                                    oxa-17,17-dimethyl-                                                           prostanoic acid                                        1808    1816           8β,15-dimethyl-9α/β,15-                                       dihydroxy-prostanoic                                                          acid                                                   1809    1817           8β,15-dimethyl-9-oxo-                                                    15-hydroxy-prostanoic                                                         acid                                                   1810    1819           8α,15-dimethyl-9-oxo-                                                   15-hydroxy-8-iso-                                                             prostanoic acid                                        1811    1834           8β,15-dimethyl-9α/β,                                          11α,15-trihydroxy-                                                      prostanoic acid                                        1812    1835           8β,15-dimethyl-9-oxo-                                                    11α,15-dihydroxy-                                                       prostanoic acid                                        1813    1837           8α,15-dimethyl-9-oxo-                                                   11α,15-dihydroxy-8-                                                     iso-prostanoic acid                                    1814    1843           8β,15-dimethyl-9-oxo-                                                    11α,15-dihydroxy-7a,                                                    7b-bishomo-prostenoic                                                         acid                                                   1815    1849           8β,15-dimethyl-9-oxo-                                                    11α,15-dihydroxy-3-                                                     oxa-prostanoic acid                                    ______________________________________                                    

EXAMPLES 1816-1859

Treatment by the procedure described in Example 1082 of the8-methyl-9α/β,15-dihydroxy-prostenoic acids listed in Table 45 belowsuccessively with 2,3-dichloro-5,6-dicyanobenzoquinone to give thecorresponding 15-keto derivatives; 2.4 equivalents each of triethylamineand trimethylsilyl chloride to give the corresponding9α/β-O-trimethylsilyl ether trimethylsilyl prostenoate ester in theinstance of the 11α-hydroxy derivatives an additional 1.1 equivalenteach of triethylamine and trimethylsilyl chloride is used and the11α-O-trimethylsilyl ether derivative is obtained); methyl magnesiumbromide to give the 15-methyl-15-hydroxy bis or tris trimethylsilylblocked ether-ester; mehanol-water-acetic acid for deblocking of thetrimethylsilyl ether and ester blocking groups to give the listed9α/β-hydroxy-15-methyl-15-hydroxy derivatives. In the 11-deoxy seriestreatment of these 9α/β-hydroxy-15-methyl-15-hydroxy products withCollins reagent in methylene chloride provides the corresponding11-deoxyl-9-oxo-15-hydroxy-15-methyl-prostenoic acids, also listed inthe table. In the 11α-hydroxy series, treatment of the 9α/β,11α-15-trihydroxy-15-methyl derivatives with 1.1 molar equivalents each oftriethylamine and trimethylsilyl chloride provides the corresponding11α-O-trimethylsilyloxy-9α/β,15-dihydroxy derivative, which on oxidationin the usual way with Collins reagent in methylene chloride followed bysilyl ether cleavage (treatment with methanol-water-acetic acid by theprocedure described in Example 1082) provides the corresponding9-oxo-11α,15-dihydroxy-15-methyl-prostenoic acids of the Table.

                  TABLE 45                                                        ______________________________________                                                Starting 9α/β,(or                                                  9α),15-dihydroxy-                                                       or 9α/β (or 9α),                                                            Product                                                        11α,15-trihydroxy                                                                      8,15-dimethyl-15-hy-                                   Ex-     derivative of  droxy-prostanoic                                       ample   Example        acids                                                  ______________________________________                                        1816    1659           8β,15-dimethyl-9α,β,15-                                       dihydroxy-13-trans-                                                           prostenoic acid                                        1817    1659           8β,15-dimethyl-9-oxo-                                                    15-hydroxy-13-trans-                                                          prostenoic acid                                        1818    1660           8α,15-dimethyl-9α,15-                                             dihydroxy-8-iso-13-                                                           trans-prostenoic acid                                  1819    1660           8α,15-dimethyl-9-oxo-                                                   15-hydroxyl-8-iso-13-                                                         trans-prostenoic acid                                  1820    1730           8β,15-dimethyl-9α/β,15-                                       dihydroxy-13-trans,17-                                                        cis-prostadienoic acid                                 1821    1730           8β,15-dimethyl-9-oxo-                                                    15-hydroxy-13-trans-                                                          17-cis-prostadienoic                                                          acid                                                   1822    1731           8α,15-dimethyl-9α/β,15-                                      dihydroxy-8-iso-13-                                                           trans,17-cis-prosta-                                                          dienoic acid                                           1823    1731           8α,15-dimethyl-9-oxo-                                                   15-hydroxy-8-iso-13-                                                          trans,17-cis-prosta-                                                          dienoic acid                                           1824    1738           8β,15-dimethyl-9α/β,                                          15-dihydroxy-7a,7b-                                                           bishomo-13-trans-                                                             prostenoic acid                                        1825    1738           8β,15-dimethyl-9-oxo-                                                    15-hydroxy-7a,7b-bis-                                                         homo-13-trans-prost-                                                          enoic acid                                             1826    1746           8β,15-dimethyl-9α/β,                                          15-dihydroxy-3-oxa-16,                                                        16-dimethyl-13-trans-                                                         prostenoic acid                                        ______________________________________                                                Starting 9α/β,(or                                                  9α),15-dihydroxy-                                                       or 9α/β  (or 9α),                                                           Product                                                        11α,15-dihydroxy                                                                       8,15-dimethyl-15-hy-                                   Ex-     derivative of  droxy-prostenoic                                       ample   Example        acids                                                  ______________________________________                                        1827    1746           8β,15-dimethyl-9-oxo-                                                    15-hydroxy-3-oxa-16,                                                          16-dimethyl-13-trans-                                                         prostenoic acid                                        1828    1750           8β,15-dimethyl-9α/β,                                          15-dihydroxy-3-oxa-                                                           13-trans,17-cis-                                                              prostadienoic acid                                     1829    1750           8β,15-dimethyl-9-oxo-                                                    15-hydroxy-3-oxa-13-                                                          trans,17-cis-prosta-                                                          dienoic acid                                           1830    1770           8β,15-dimethyl-9α/β,                                          15-dihydroxy-5-cis,                                                           13-trans,17-cis-prosta-                                                       trienoic acid                                          1831    1770           8β,15-dimethyl-9-oxo-                                                    15-hydroxy-5-cis,13-                                                          trans,17-cis-prosta-                                                          trienoic acid                                          1832    1778           8β,15-dimethyl-9α/β,                                          15-dihydroxy-20-ethyl-                                                        5-cis,13-trans-                                                               prostadienoic acid                                     1833    1778           8β,15-dimethyl-9-oxo-                                                    15-hydroxy-20-ethyl-5-                                                        cis,13-trans-prosta-                                                          dienoic acid                                           1834    1523           8β,15-dimethyl-9α/β,                                          11α,15-trihydroxy-13-                                                   trans-prostenoic acid                                  1835    1523           8β,15-dimethyl-9-oxo-                                                    11α,15-dihydroxy-13-                                                    trans-prostenoic acid                                  1836    1524           8α,15-dimethyl-9α/β,                                         11α,15-trihydroxy-8-                                                    iso-13-trans-pros-                                                            tenoic acid                                            1837    1524           8α,15-dimethyl-9-oxo-                                                   11α,15-dihydroxy-                                                       8-iso-13-trans-                                                               prostenoic acid                                        1838    1535           8β,15-dimethyl-9α/β,                                          11α,15-trihydroxy-13-                                                   trans,17-cis-prosta-                                                          dienoic acid                                           1839    1535           8β,15-dimethyl-9-oxo-                                                    11α,15-dihydroxy-13-                                                    trans,17-cis-prosta-                                                          dienoic acid                                           1840    1539           8β,15-dimethyl-9α/β,                                          11α,15-trihydroxy-20-                                                   ethyl-13-trans-pro-                                                           stenoic acid                                           1841    1539           8β,15-dimethyl-9-oxo-                                                    11α,15-dihydroxy-20-                                                    ethyl-13-trans-pro-                                                           stenoic acid                                           1842    1551           8β,15-dimethyl-9α/β,                                          11α,15-trihydroxy-7a,                                                   7b-bishomo-13-trans-                                                          prostenoic acid                                        1843    1551           8β,15-dimethyl-9-oxo-                                                    11α,15-dihydroxy-7a,                                                    7b-bishomo-13-trans-                                                          prostenoic acid                                        1844    1555           8β,15-dimethyl-9α/β,                                          11α,15-trihydroxy-2-                                                    ethyl-13-trans-                                                               prostenoic acid                                        1845    1555           8β,15-dimethyl-9-oxo-                                                    11α,15-dihydroxy-2-                                                     ethyl-13-trans-                                                               prostenoic acid                                        1846    1559           8β,15-dimethyl-9α/β,                                          11α,15-trihydroxy-3,3,                                                  20-trimethyl-13-trans-                                                        prostenoic acid                                        1847    1559           8β,15-dimethyl-9-oxo-                                                    11α,15-dihydroxy-3,3,                                                   20-trimethyl-13-trans-                                                        prostenoic acid                                        1848    1563           8β,15-dimethyl-9α/β,                                          11α,15-trihydroxy-3-                                                    oxa-13-trans-prostenoic                                                       acid                                                   1849    1563           8β,15-dimethyl-9-oxo-                                                    11α,15-dihydroxy-3-                                                     oxa-13-trans-prostenoic                                                       acid                                                   1850    1571           8β,15-dimethyl-9α/β,                                          11α,15-trihydroxy-3-                                                    oxa-13-trans,17-cis-                                                          prostadienoic acid                                     1851    1571           8β,15-dimethyl-9-oxo-                                                    11α,15-dihydroxy-3-oxa-                                                 13-trans,17-cis-prosta-                                                       dienoic acid                                           1852    1599           8β,15-dimethyl-9α/β,                                          11α,15-trihydroxy-5-                                                    cis,13-trans-prosta-                                                          dienoic acid                                           1853    1599           8β,15-dimethyl-9-oxo-                                                    11α,15-dihydroxy-5-                                                     cis,13-trans-prosta-                                                          dienoic acid                                           1854    1603           8β,15-dimethyl-9α/β,                                          11α,15-trihydroxy-5-cis,                                                13-trans,17-cis-prosta-                                                       trienoic acid                                          1855    1603           8β,15-dimethyl-9-oxo-                                                    11α,15-dihydroxy-5-                                                     cis,13-trans,17-cis-                                                          prostatrienoic acid                                    1856    1611           8β,15-dimethyl-9α/β,                                          11α,15-trihydroxy-4-nor-                                                20-methyl-5-cis,13-                                                           trans-prostadienoic                                                           acid                                                   1857    1611           8β,15-dimethyl-9-oxo-                                                    11α,15-dihydroxy-4-                                                     nor-20-methyl-5-cis,                                                          13-trans-prostadienoic                                                        acid                                                   1858    1623           8β,15-dimethyl-9α/β,                                          11α,15-trihydroxy-4a,                                                   4b-bishomo-5-cis,13-                                                          trans,17-cis-prosta-                                                          trienoic acid                                          1859    1623           8β,15-dimethyl-9-oxo-                                                    11α,15-dihydroxy-4a,                                                    4b-bishomo-5-cis,13-                                                          trans,17-cis-prosta-                                                          trienoic acid                                          ______________________________________                                    

EXAMPLES 1860-1876

Treatment of the 8,15-dimethyl-9-oxo-11α-hydroxy derivatives listed inTable 46 below with aqueous acetic acid by the procedure described inExample 1387 is productive of the corresponding 10-prostenoic acidproducts of the table.

                  TABLE 46                                                        ______________________________________                                                Starting 8,15-di-                                                             methyl-9-oxo-11α-                                                                       Product                                               Ex-     hydroxy deriva- 8,15-dimethyl-9-oxo-                                  ample   tives of Example                                                                              10-prostenoic acid                                    ______________________________________                                        1860    1835            8β,15-dimethyl-9-oxo-                                                    15-hydroxy-10,13-trans-                                                       prostadienoic acid                                    1861    1837            8α,15-dimethyl-9-oxo-                                                   15-hydroxy-8-iso-10,                                                          13-trans-prostadienoic                                                        acid                                                  1862    1839            8β,15-dimethyl-9-oxo-                                                    15-hydroxy-10,13-trans,                                                       17-cis-prostatrienoic                                                         acid                                                  1863    1841            8β,15-dimethyl-9-oxo-                                                    15-hydroxy-20-ethyl-                                                          10,13-trans-prosta-                                                           dienoic acid                                          1864    1843            8β,15-dimethyl-9-oxo-                                                    15-hydroxy-7a,7b-bis-                                                         homo-10,13-trans-                                                             prostadienoic acid                                    1865    1845            8β,15-dimethyl-9-oxo-15-                                                 hydroxy-2-ethyl-10,13-                                                        trans-prostadienoic                                                           acid                                                  1866    1847            8β,15-dimethyl-9-oxo-                                                    15-hydroxy-3,3,20-tri-                                                        methyl-10,13-trans-                                                           prostadienoic acid                                    1867    1849            8β,15-dimethyl-9-oxo-                                                    15-hydroxy-3-oxa-10,13-                                                       trans-prostadienoic                                                           acid                                                  1868    1851            8β,15-dimethyl-9-oxo-                                                    15-hydroxy-3-oxa-10,                                                          13-trans,17-cis-prosta-                                                       trienoic acid                                         1869    1853            8β,15-dimethyl-9-oxo-                                                    15-hydroxy-5-cis,10,13-                                                       trans-prostatrienoic                                                          acid                                                  1870    1855            8β,15-dimethyl-9-oxo-                                                    15-hydroxy-5-cis,10,                                                          13-trans,17-cis-prosta-                                                       tetraenoic acid                                       1871    1857            8β,15-dimethyl-9-oxo-                                                    15-hydroxy-4-nor-20-                                                          methyl-5-cis,10,13-                                                           trans-prostatrienoic                                                          acid                                                  1872    1859            8β,15-dimethyl-9-oxo-                                                    15-hydroxy-4a,4b-bis-                                                         homo-5-cis,10,13-trans,                                                       17-cis-prostatetraenoic                                                       acid                                                  1873    1812            8β,15-dimethyl-9-oxo-15-                                                 hydroxy-10-prostenoic                                                         acid                                                  1874    1815            8β,15-dimethyl-9-oxo-15-                                                 hydroxy-3-oxa-10-                                                             prostenoic acid                                       1875    1814            8β,15-dimethyl-9-oxo-15-                                                 hydroxy-7a,7b-bishomo-                                                        10-prostenoic acid                                    1876    1813            8α,15-dimethyl-9-oxo-                                                   15-hydroxy-8-iso-10-                                                          prostenoic acid                                       ______________________________________                                    

EXAMPLE 1877 Preparation of 3-methoxy-1-octyne

To an ice-cooled solution of 63 g. of 1-octyn-3-ol in 300 ml. ofdimethoxyethane is added under an inert atmosphere 312 ml. of 1.6 Mn-butyllithium in hexane dropwise over 1 hour. To the mixture is thenadded 145 g. of methyl iodide and the resulting mixture is stirred atambient temperatures for 24 hours and then heated to 60° C. for 1 hour.The mixture is cooled and poured into cold dilute hydrochloric acid. Theorganic phase is separated, washed with water and saturated brine, dried(Na₂ SO₄), and evaporated to an oil, dried (Na₂ SO₄), and evaporated toan oil. Fractional distillation of the oil in vacuo yields the productas a colorless oil.

EXAMPLE 1878 Preparation of 1-Iodo-3-methoxy-trans-1-octene

Treatment of 3-methoxy-1-octyne (Example 1877) with disiamylborane,trimethylamine oxide, sodium hydroxide and iodine by the proceduredescribed in Examle 996 furnishes the title product.

EXAMPLE 1879 Preparation of 3-Methoxy-trans-1-octenyl lithium

Treatment of 1-iodo-3-methoxy-trans-1-octene (Example 1878) with butyllithium in the manner of Example 961 provides a toluene-hexane solutionof the subject trans-vinyl lithium derivative.

EXAMPLE 1880 Preparation of Lithium(3-methoxy-trans-1-octenyl)trimethylalanate

The subject alanate in hydrocarbon solution is prepared according to themethod of Example 963 from a hydrocarbon solution of3-methoxy-trans-1-octenyl lithium (Example 1879) and trimethylaluminum.

EXAMPLES 1881-1895

Treatment of the cycloalkenones listed in Table 47 withlithium(3-methoxy-trans-1-octenyl)trimethylalanate (Example 1880) by theprocedure described in Example 957 with the omission of the 80% aqueousacetic acid treatment (80° C., 1 hour) followed by saponification of theintermediate alkyl prostenoates by the procedure described in Example122 furnishes the product 9-oxo-15-methoxy-13-trans-prostenoic acids ofthe table.

                  TABLE 47                                                        ______________________________________                                                Starting cyclo-                                                                              Product 9-oxo-15-                                      Ex-     alkenone of    methoxy-13-trans-                                      ample   Example        prostenoic acid                                        ______________________________________                                        1881    23             9-oxo-7a,7b-bishomo-                                                          15-methoxy-13-trans-                                                          prostenoic acid                                        1882    31             9-oxo-2-ethyl-15-                                                             methoxy-13-trans-pro-                                                         stenoic acid                                           1883    41             9-oxo-3,3-dimethyl-                                                           15-methoxy-13-trans-                                                          prostenoic acid                                        1884    46             9-oxo-3-oxa-15-methoxy-                                                       13-trans-prostenoic                                                           acid                                                   1885    53             9-oxo-7-nor-15-methoxy-                                                       13-trans-prostenoic                                                           acid                                                   1886    70             9-oxo-2-fluoro-15-                                                            methoxy-13-trans-                                                             prostenoic acid                                        1887    74             9-oxo-7a-homo-15-                                                             methoxy-13-trans-pro-                                                         stenoic acid                                           1888    79             9-oxo-2-phenyl-15-                                                            methoxy-13-trans-pro-                                                         stenoic acid                                           1889    99             9-oxo-2-methyl-15-                                                            methoxy-13-trans-pro-                                                         stenoic acid                                           1890    111            9-oxo-10a-homo-15-                                                            methoxy-13-trans-                                                             prostenoic acid                                        1891    118            9-oxo-3-thia-15-                                                              methoxy-13-trans-                                                             prostenoic acid                                        1892    900            9-oxo-15-methoxy-5-                                                           cis,13-trans-pro-                                                             stadienoic acid                                        1893    1144           9-oxo-4-nor-15-methoxy-                                                       13-trans-prostadienoic                                                        acid                                                   1894    1145           9-oxo-4-homo-15-                                                              methoxy-5-cis,13-                                                             trans-prostadienoic                                                           acid                                                   1895    1146           9-oxo-4a,4b-bishomo-                                                          15-methoxy-13-trans-                                                          prostadienoic acid                                     ______________________________________                                    

EXAMPLES 1896-1910

Treatment of the 9-oxo-15-methoxy-13-trans-prostenoic acids listed inTable 48 below with lithium perhydro-9b-boraphenalylhydride by theprocedure described in Example 737 furnishes the9α-hydroxy-15-methoxy-13-trans-prostenoic acids of the Table.

                  TABLE 48                                                        ______________________________________                                                Starting 9-oxo-                                                               15-methoxy-13-                                                                trans-prosten- Product 9α-hydroxy-15-                           Ex-     oic acid of    methoxy-13-trans-                                      ample   Example        prostenoic acid                                        ______________________________________                                        1896    1881           9α-hydroxy-7a,7b-bis-                                                   homo-15-methoxy-13-                                                           trans-prostenoic acid                                  1897    1882           9α-hydroxy-2-ethyl-                                                     15-methoxy-13-trans-                                                          prostenoic acid                                        1898    1883           9α-hydroxy-3,3-dimethyl-                                                15-methoxy-13-trans-                                                          prostenoic acid                                        1899    1884           9α-hydroxy-3-oxa-15-                                                    methoxy-13-trans-                                                             prostenoic acid                                        1900    1885           9α-hydroxy-7-nor-15-                                                    methoxy-13-trans-pro-                                                         prostenoic acid                                        1901    1886           9α-hydroxy-2-fluoro-                                                    15-methoxy-13-trans-                                                          prostenoic acid                                        1902    1887           9α-hydroxy-7a-homo-                                                     15-methoxy-13-trans-                                                          prostenoic acid                                        1903    1888           9α-hydroxy-2-phenyl-                                                    15-methoxy-13-trans-                                                          prostenoic acid                                        1904    1889           9α-hydroxy-2-methyl-                                                    methoxy-13-trans-                                                             prostenoic acid                                        1905    1890           9α-hydroxy-10a-homo-                                                    15-methoxy-13-trans-                                                          prostenoic acid                                        1906    1891           9α-hydroxy-3-thia-15-                                                   methoxy-13-trans-                                                             prostenoic acid                                        1907    1892           9α-hydroxy-15-methoxy-                                                  5-cis,13-trans-prosta-                                                        dienoic acid                                           1908    1893           9α-hydroxy-4-nor-15-                                                    methoxy-5-cis,13-                                                             trans-prostadienoic                                                           acid                                                   1909    1894           9α-hydroxy-4-homo-15-                                                   methoxy-5-cis,13-trans-                                                       prostadienoic acid                                     1910     1895β    9α-hydroxy-4a,4b-bis-                                                   homo-15-methoxy-13-                                                           trans-prostenoic acid                                  ______________________________________                                    

EXAMPLE 1911 Preparation of2-(6-carboxy-2-cis-hexenyl)-3,4-oxidocyclopentanol

A solution of 5.0 g. (35 mmoles) of5-hydroxy-2,3-oxidocyclopentylacetaldehyde-γ-lactol (isomeric mixture;E. J. Corey and R. Noyori, Tetrahedron Letters, 1970, 311) in 25 ml. ofDMSO is added during 0.5 minutes at 20° C. to a stirred solution of theWithig reagent [E. J. Corey et al., JACS, 91 5675 (1969); also Example1108] and dimsyl sodium prepared from 23.5 g. (53 mmoles) of4-carboxybutyltriphenylphosphonium bromide, 6.1 g. (140 mmoles) of 57%sodium hydride dispersion, and 230 ml. of DMSO (dimethylsulfoxide).

The solution is stirred at ambient temperatures for 2 hours and pouredinto a stirred mixture of methylene chloride, ice, and hydrochloricacid. The reaction mixture is worked up as described in Example 1105,and the crude product is purified by dry column chromatography on silicagel to provide the title compound (mixture of two stereoisomers) as anoil, IR (film) 3450, 1710, and 832 cm⁻¹.

EXAMPLE 1912 Preparation of2-(6-carboxy-2-cis-hexenyl)-3,4-oxidocyclopentanone

A stirred solution of 2.98 g. (13.2 mmoles) of2-(6-carboxy-2-cis-hexenyl)-3,4-oxidocyclopentanol (Example 1911) in 66ml. of acetone is treated dropwise with 3.30 ml. of 8 N chromic acid in8 N M₂ SO₄ during 20 minutes at -10° to -5° C. The solution is stirredat -5° C. for 10 minutes and treated successively with a few drops ofisopropanol and 12 ml. of water. The mixture is filtered, and thefiltrate is concentrated saturated with sodium chloride, and extractedwith ethyl acetate. The extract is washed with brine, dried over MgSO₄,and evaporated to give an oil, IR (film) 1740, 1710, and 840 cm⁻¹.

EXAMPLE 1913 Preparation of2-(6-carboxy-2-cis-hexenyl)-4-hydroxycyclopent-2-en-1-one

A solution of (pH or 10.2-10.5) of 2.42 g. (10.8 mmoles) of2-(6-carboxy-2-cis-hexenyl)-3,4-oxidocyclopentanone (Example 1912) 4.58g. (43.2 mmoles) of sodium carbonate, and 216 ml. of water is allowed tostand at room temperatures under nitrogen for 24 hours. The solution isacidified at 15° C. with hydrochloric acid and extracted with ethylacetate. The extract is washed with brine, dried over MgSO₄, andevaporated to give an oil; IR (film) 1700 (carbonyl groups) and 1630cm⁻¹ (conjugated olefin); NMR 7.11 (1), 5.54 (2), and 4.95 (1)δ.

We claim:
 1. A compound selected from the group consisting of those ofthe formulae: ##STR38## wherein W is selected from the group consistingof triphenylmethyl, X is selected from the group consisting of chloroand bromo; and R₂ is selected from the group consisting of a straightchain alkyl group having from 2 to 10 carbon atoms, a straight chainalkyl group having from 2 to 10 carbon atoms, and substituted with analkyl group having from one to three carbon atoms, a straight chainalkenyl group having from 2 to 10 carbon atoms and substituted with oneor two alkyl groups having between them 2 to 5 carbon atoms, and astraight chain alkynyl group having from 2 to 10 carbon atoms.
 2. Thecompound according to claim 1 formula I thereof, wherein X is bromo, R₂is n-pentyl, and W is triphenylmethyl;3-triphenylmethoxy-trans-1-octenyl magnesium bromide.
 3. The compoundaccording to claim 1 formula II thereof, wherein X is bromo, R₂ isn-pentyl and W is triphenylmethyl; 3-triphenylmethoxy-cis-1-octenylmagnesium bromide.